WO2021052503A1 - 一种多能干细胞、药物组合物及其制备方法与用途 - Google Patents

一种多能干细胞、药物组合物及其制备方法与用途 Download PDF

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WO2021052503A1
WO2021052503A1 PCT/CN2020/116626 CN2020116626W WO2021052503A1 WO 2021052503 A1 WO2021052503 A1 WO 2021052503A1 CN 2020116626 W CN2020116626 W CN 2020116626W WO 2021052503 A1 WO2021052503 A1 WO 2021052503A1
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mesenchymal stem
stem cell
less
injection
cell population
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PCT/CN2020/116626
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English (en)
French (fr)
Chinese (zh)
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周琪
胡宝洋
郝捷
李伟
吴骏
王柳
郭保杰
李仲文
高婷婷
陈燕霞
王红梅
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北京干细胞与再生医学研究院
中国科学院动物研究所
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Application filed by 北京干细胞与再生医学研究院, 中国科学院动物研究所 filed Critical 北京干细胞与再生医学研究院
Priority to KR1020227013086A priority Critical patent/KR20220094194A/ko
Priority to US17/761,990 priority patent/US20220348879A1/en
Priority to EP20864985.5A priority patent/EP4047083A4/en
Priority to JP2022518395A priority patent/JP2022548997A/ja
Publication of WO2021052503A1 publication Critical patent/WO2021052503A1/zh

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Definitions

  • the present invention relates to the field of cell therapy. Specifically, the present invention relates to a method for producing a mesenchymal stem cell population, the mesenchymal stem cell population and the culture supernatant thereof produced by the method, and a pharmaceutical composition containing such cells or the culture supernatant thereof. The present invention also relates to the mesenchymal stem cell population and the culture supernatant thereof, as well as the use of the mesenchymal stem cell population and the culture supernatant thereof for preventing and/or treating diseases.
  • MSC Mesenchymal stem cells
  • ESCs Embryonic stem cells
  • iPSCs induced pluripotent stem cells
  • Embryonic stem cells have the ability to proliferate indefinitely, and have the potential to differentiate into various cells and tissues of mesoderm, endoderm and ectoderm, so they can be used as a new source of MSC.
  • many studies have reported methods for inducing mesenchymal-like cells from human embryonic stem cells.
  • there are still shortcomings such as low induction efficiency, complicated induction process, and long induction time, and most of the methods require the use of heterologous serum such as serum. Substances cannot be used clinically.
  • mesenchymal stem cells In short, given that the current methods of obtaining mesenchymal stem cells are limited by some defects, it is necessary to find a method of producing mesenchymal stem cells with high purity, high yield and short time, which can be used for clinical treatment and prevention of various diseases. It is very necessary.
  • the inventor of the present application has obtained a method for in vitro production of mesenchymal stem cells from stem cells (such as pluripotent stem cells or pluripotent stem cells) through a large number of experiments and repeated explorations.
  • the mesenchymal stem cells obtained by this method have significantly improved The amount of cytokine secretion, and thus completed the present invention.
  • the cell of the present invention or the cell obtained by the method of the present invention may be referred to as M cell.
  • the present invention provides a mesenchymal stem cell population, wherein the average MMP1 expression level of the mesenchymal stem cell population (for example, without genetic modification) is that of primary mesenchymal stem cells.
  • At least about 10 times e.g., at least about 20 times, at least about 30 times, at least about 40 times, at least about 50 times, at least about 60 times, at least about 70 times, at least about 80 times, at least about 90 times, At least about 100 times, at least about 150 times, at least about 200 times, at least about 300 times, at least about 400 times, at least about 500 times, at least about 1000 times, at least about 2000 times, at least about 3000 times, at least about 5000 times, At least about 8000 times, at least about 10000 times, or at least about 12000 times); and/or, the average PGE2 expression level of the mesenchymal stem cell population (for example, in the absence of genetic modification) is that of primary mesenchymal stem cells At least about 10-fold (e.
  • primary mesenchymal stem cells refers to mesenchymal stem cells directly isolated from tissues (such as adipose tissue, umbilical cord, bone marrow, or cord blood) taken out of the body.
  • the MMP1 expression level of the mesenchymal stem cell population is at least about 10 times (eg, at least about 50 times, at least about 100 times, at least about 200 times that of the same number of primary mesenchymal stem cells). , At least about 300 times, at least about 400 times, at least about 500 times, at least about 1000 times, at least about 2000 times, at least about 3000 times, at least about 5000 times, at least about 8000 times, at least about 10000 times, or at least about 12000 Times).
  • the PGE2 expression level of the mesenchymal stem cell population is at least about 10 times (eg, at least about 20 times, at least about 30 times, at least about 50 times that of the same number of primary mesenchymal stem cells). , At least about 60 times, or at least about 80 times). In certain embodiments, the PGE2 expression level of the mesenchymal stem cell population is about 80 times that of the same number of primary mesenchymal stem cells.
  • the average PD-L1 expression level of the mesenchymal stem cell population (for example, without genetic modification) is higher than Primary mesenchymal stem cells.
  • the average PD-L1 expression level of the mesenchymal stem cell population is at least about 2 times that of primary mesenchymal stem cells (e.g. , At least about 3 times).
  • the average PD-L1 expression level of the mesenchymal stem cell population is about 3 times that of primary mesenchymal stem cells.
  • the PD-L1 expression level of the mesenchymal stem cell population is at least about 2 times that of the same number of primary mesenchymal stem cells (For example, at least about 3 times). In certain embodiments, after stimulation with 50-100 ng/ml IFN- ⁇ , the PD-L1 expression level of the mesenchymal stem cell population is about 3 times that of the same number of primary mesenchymal stem cells.
  • the average IDO expression level of the population of mesenchymal stem cells is higher than that of primary mesenchymal stem cells.
  • the average IDO expression level of the mesenchymal stem cell population is at least about 10 times (eg, at least about 20 times, at least about 30 times, at least about 50 times, at least about About 60 times, at least about 80 times, at least about 100 times, or at least about 110 times).
  • the average IDO expression level of the mesenchymal stem cell population is about 110 times that of primary mesenchymal stem cells.
  • the IDO expression level of the mesenchymal stem cell population is at least about 10 times (eg, at least about 20 times, at least about 30 times, at least about 50 times that of the same number of primary mesenchymal stem cells). , At least about 60 times, at least about 80 times, at least about 100 times, or at least about 110 times). In certain embodiments, the IDO expression level of the mesenchymal stem cell population is about 110 times that of the same number of primary mesenchymal stem cells.
  • the expression can be monitored by measuring the level of the full-length mRNA, mRNA fragment, full-length protein, or protein fragment of the gene. Therefore, in certain embodiments, the expression level is mRNA level or protein level.
  • the expression is assessed by analyzing the expression of mRNA transcripts of the gene. For example, the presence or content of IDO, MMP1, PDL1 or PGE2 mRNA in the cell population is determined by RT-PCR to determine the expression of the above-mentioned genes in the cell population.
  • the expression is assessed by analyzing the expression of the protein product of the gene. For example, the presence or content of IDO, MMP1, PDL1 or PGE2 protein in the culture supernatant of the cell population is determined by immunological detection to determine the expression of the above-mentioned genes in the cell population. Therefore, in certain embodiments, the expression level of the gene (eg, IDO, MMP1, PDL1, or PGE2) is evaluated by the level of the corresponding protein secreted in the culture supernatant.
  • the expression level of the gene eg, IDO, MMP1, PDL1, or PGE2
  • the mesenchymal stem cell population has one or more of the above-mentioned gene expression characteristics without genetic modification, and the term “eptetically modified” refers to that it has not undergone DNA Or the process of adding exogenous genetic material in the form of RNA to the total genetic material of a cell.
  • exogenous genetic material may refer to an artificially introduced nucleotide sequence, which is relative to a cell that has not been genetically modified. foreign.
  • the mesenchymal stem cell population of the present invention may contain one or more genetic modifications.
  • the population of mesenchymal stem cells is derived from stem cells.
  • the stem cell is a pluripotent stem cell or a pluripotent stem cell.
  • the pluripotent stem cells are selected from embryonic stem cells, haploid stem cells, induced pluripotent stem cells, or adult stem cells.
  • the mesenchymal stem cell population is produced from embryonic stem cells or induced pluripotent stem cells.
  • the population of mesenchymal stem cells is produced in vitro.
  • the mesenchymal stem cell population also has the following characteristics:
  • Cells containing ⁇ 80% express CD105, CD73, CD90, CD13 , CD29, CD44, CD166 and HLA-ABC one or more;
  • Cells containing ⁇ 2% express CXCL1, CD34, CD45, CD133, FGFR2, CD271, Stro-1 and CXCR4 One or more of.
  • the mesenchymal stem cell population also has one or more of the following characteristics:
  • the proportion of CD274+ cells is not less than 80%, such as 80%-95%, such as about 80%, about 85%, about 86%, about 87%, about 88%, about 89%. %, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95%.
  • the proportion of the CD24+ cells is not less than 50%, such as 50%-70%, such as about 50%, about 55%, about 56%, about 57%, about 58%, about 59%. %, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, or about 70%.
  • the proportion of CD31+ cells is not less than 5%, such as 5%-20%, such as about 5%, about 10%, about 12%, about 15%, about 18%, or about 20%.
  • the mesenchymal stem cell population of the present invention can be formulated and administered as a pharmaceutical composition.
  • a pharmaceutical composition may be in any form known in the medical field, and is preferably an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • sterile isotonic aqueous or non-aqueous solution e.g., balanced salt solution or physiological saline
  • dispersion e.g., balanced salt solution or physiological saline
  • the present invention provides a method for producing a mesenchymal stem cell population, or the method for producing a mesenchymal stem cell population according to the first aspect, which includes the following steps:
  • the first culture medium is a basic medium supplemented with the following substances: one or more serum substitutes, one or more non-essential amino acids , Glutamine or L-alanyl-L-glutamine stabilized dipeptide, and bFGF;
  • the second medium is a basic medium supplemented with the following substances: one or more serum substitutes, One or more non-essential amino acids, a stabilized dipeptide of glutamine or L-alanyl-L-glutamine, and one or more growth factors.
  • step (2) includes: attaching the embryoid body to a culture container and culturing using a second medium.
  • basic medium refers to any medium capable of supporting cell growth, usually containing inorganic salts, vitamins, glucose, buffer systems and essential amino acids, and usually having an osmotic pressure of about 280-330 mOsmol.
  • the stem cell described in step (1) is a pluripotent stem cell or a pluripotent stem cell.
  • the pluripotent stem cells are selected from embryonic stem cells, haploid stem cells, induced pluripotent stem cells, or adult stem cells.
  • the first medium has one or more of the following characteristics:
  • the total content of the one or more serum substitutes is 3-30% (v/v), such as about 3% (v/v), about 5% (v/v), about 8% ( v/v), about 10% (v/v), about 12% (v/v), about 15% (v/v), about 18% (v/v), about 20% (v/v), About 22% (v/v), about 25% (v/v), about 28% (v/v) or about 30% (v/v);
  • each of the one or more non-essential amino acids is 0.1-0.5 mM, for example, about 0.1 mM, about 0.2 mM, about 0.3 mM, about 0.4 mM, or about 0.5 mM;
  • the content of the stabilized dipeptide of glutamine or L-alanyl-L-glutamine is 1-5 mM, for example, about 1 mM, about 2 mM, about 3 mM, about 4 mM, or about 5 mM;
  • the content of bFGF is 1-100ng/mL, such as 2-100ng/mL, 2-50ng/mL, 5-100ng/mL, 5-50ng/mL, or 5-20ng/mL; for example, about 1ng/mL , About 2ng/mL, about 3ng/mL, about 5ng/mL, about 8ng/mL, about 10ng/mL, about 15ng/mL, about 20ng/mL, about 25ng/mL, about 30ng/mL, about 35ng/mL , About 40ng/mL, about 45ng/mL, about 50ng/mL, about 55ng/mL, about 60ng/mL, about 65ng/mL, about 70ng/mL, about 75ng/mL, about 80ng/mL, about 85ng/mL , About 90ng/mL, about 95ng/mL, or about 100ng/mL.
  • the first medium has one or more of the following characteristics:
  • the serum substitute is selected from KOSR, MSC serum-free additives, Ultraser TM G, and any combination thereof; preferably, the serum substitute is KnockOut TM SR (for example, Thermo: Product No. 10828028) (hereinafter referred to as KOSR) );
  • the non-essential amino acid is selected from glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, L-serine and combinations thereof;
  • the basic medium is selected from KnockOut TM DMEM (for example, Gibco: article number 10829018) (hereinafter referred to as KO-DMEM), KnockOut TM DMEM/F-12 (for example, Gibco: article number 12660-012) (hereinafter referred to as KO-DMEM/F12), DMEM, ⁇ -MEM, F-12, MEM, BME, RPMI 1640, G-MEM and any combination thereof; preferably, the basic medium is selected from KO-DMEM, KO-DMEM /F12, DMEM, DMEM/F12; Preferably, the basic medium is KO-DMEM.
  • the first medium includes: KO-DMEM, KOSR, glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L- Stabilized dipeptide of proline, L-serine, L-alanyl-L-glutamine, and bFGF.
  • the first medium contains: 3-30% (v/v) KOSR, 1-5 mM L-alanyl-L-glutamine stabilized dipeptide, 1- 100ng/mL bFGF, and the following amino acids each at a concentration of 0.1-0.5mM: glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline , L-serine.
  • the first medium further comprises ⁇ -mercaptoethanol.
  • the content of ⁇ -mercaptoethanol is 0.1-0.5% (v/v), such as about 0.1% (v/v), about 0.2% (v/v), about 0.3% (v/v) ), about 0.4% (v/v) or about 0.5% (v/v).
  • the first medium consists essentially of the following components: KO-DMEM, KOSR, glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamine Stabilized dipeptide of acid, L-proline, L-serine, L-alanyl-L-glutamine, bFGF and ⁇ -mercaptoethanol.
  • the first medium contains: 3-30% (v/v) KOSR, 1-5 mM L-alanyl-L-glutamine stabilized dipeptide, 1- 100ng/mL bFGF, 0.1-0.5% (v/v) ⁇ -mercaptoethanol, and the following amino acids each at a concentration of 0.1-0.5mM: glycine, L-alanine, L-asparagine, L-day Partic acid, L-glutamic acid, L-proline, L-serine.
  • the first medium comprises: about 15% (v/v) of KOSR, about 1 mM of stabilized dipeptide of L-alanyl-L-glutamine, about 8 ng/mL BFGF, about 0.1% (v/v) ⁇ -mercaptoethanol, and the following amino acids at a concentration of about 0.1 mM each: glycine, L-alanine, L-asparagine, L-aspartic acid, L -Glutamic acid, L-proline, L-serine.
  • the first medium comprises: about 18% (v/v) of KOSR, about 1 mM of stabilized dipeptide of L-alanyl-L-glutamine, about 12 ng/mL BFGF, about 0.1% (v/v) ⁇ -mercaptoethanol, and the following amino acids at a concentration of about 0.1 mM each: glycine, L-alanine, L-asparagine, L-aspartic acid, L -Glutamic acid, L-proline, L-serine.
  • the first medium comprises: about 20% (v/v) of KOSR, about 2 mM of stabilized dipeptide of L-alanyl-L-glutamine, about 10 ng/mL BFGF, about 0.1% (v/v) ⁇ -mercaptoethanol, and the following amino acids at a concentration of about 0.1 mM each: glycine, L-alanine, L-asparagine, L-aspartic acid, L -Glutamic acid, L-proline, L-serine.
  • the first medium comprises: about 22% (v/v) of KOSR, about 2 mM of stabilized dipeptide of L-alanyl-L-glutamine, about 12 ng/mL BFGF, about 0.2% (v/v) of ⁇ -mercaptoethanol, and the following amino acids at a concentration of about 0.1 mM each: glycine, L-alanine, L-asparagine, L-aspartic acid, L -Glutamic acid, L-proline, L-serine.
  • the first medium comprises: about 22% (v/v) of KOSR, about 2 mM of stabilized dipeptide of L-alanyl-L-glutamine, about 12 ng/mL BFGF, about 0.1% (v/v) of ⁇ -mercaptoethanol, and the following amino acids at a concentration of about 0.2 mM each: glycine, L-alanine, L-asparagine, L-aspartic acid, L -Glutamic acid, L-proline, L-serine.
  • the first medium consists essentially of the following components: KO-DMEM (Gibco: article number 10829018), KOSR (Thermo: article number 10828028), NEAA (Gibco: article number 11140050), GlutaMAX (Gibco : Catalog No. A1286001), bFGF and ⁇ -mercaptoethanol.
  • the first medium comprises: 18-22% (v/v) KOSR, 0.5-1.5% (v/v) GlutaMAX, 1-100 ng/mL bFGF, 0.1 -0.5% (v/v) ⁇ -mercaptoethanol, and 1-2% (v/v) NEAA.
  • the first medium comprises: about 15% (v/v) KOSR, about 0.5% (v/v) GlutaMAX, about 8ng/mL bFGF, about 0.1% (v/v) v/v) ⁇ -mercaptoethanol, and about 1% (v/v) NEAA.
  • the first medium comprises: about 18% (v/v) KOSR, about 0.5% (v/v) GlutaMAX, about 12ng/mL bFGF, about 0.1% (v/v) v/v) ⁇ -mercaptoethanol, and about 1% (v/v) NEAA.
  • the first medium comprises: about 20% (v/v) KOSR, about 1% (v/v) GlutaMAX, about 10ng/mL bFGF, about 0.1% (v/v) v/v) ⁇ -mercaptoethanol, and about 1% (v/v) NEAA.
  • the first medium comprises: about 22% (v/v) KOSR, about 1% (v/v) GlutaMAX, about 12ng/mL bFGF, about 0.2% (v/v) v/v) ⁇ -mercaptoethanol, and about 1% (v/v) NEAA.
  • the first medium comprises: about 22% (v/v) KOSR, about 1% (v/v) GlutaMAX, about 12ng/mL bFGF, about 0.1% (v/v) v/v) ⁇ -mercaptoethanol, and about 1% (v/v) NEAA.
  • the second medium has one or more of the following characteristics:
  • the total content of the one or more serum substitutes is 1-40% (v/v), for example, 1-35% (v/v), 1-30% (v/v), 2 -30%(v/v), 5-30%(v/v), 1-20%(v/v), 2-20%(v/v), 5-20%(v/v), 1 -10% (v/v), 2-10% (v/v), or 5-10% (v/v); for example, about 1% (v/v), about 2% (v/v), about 3% (v/v), about 5% (v/v), about 8% (v/v), about 10% (v/v), about 12% (v/v), about 15% (v/ v), about 18% (v/v), about 20% (v/v), about 22% (v/v), about 25% (v/v), about 28% (v/v), or about 30%(v/v);
  • each of the one or more non-essential amino acids is 0.1-0.5mM, such as 0.1-0.2mM, such as about 0.1mM, about 0.2mM, about 0.3mM, about 0.4mM or about 0.5mM;
  • the content of the stabilized dipeptide of glutamine or L-alanyl-L-glutamine is 1-5 mM, such as 1-3 mM, such as about 1 mM, about 2 mM, about 3 mM, about 4 mM, or about 5 mM ;
  • each of the one or more growth factors is 1-100 ng/mL, for example, about 1 ng/mL, about 2 ng/mL, about 3 ng/mL, about 5 ng/mL, about 8 ng/mL, about 10 ng /mL, about 15ng/mL, about 20ng/mL, about 25ng/mL, about 30ng/mL, about 35ng/mL, about 40ng/mL, about 45ng/mL, about 50ng/mL, about 55ng/mL, about 60ng /mL, about 65ng/mL, about 70ng/mL, about 75ng/mL, about 80ng/mL, about 85ng/mL, about 90ng/mL, about 95ng/mL, or about 100ng/mL.
  • the second medium has one or more of the following characteristics:
  • the serum substitute is selected from KOSR, MSC serum-free additives, Ultraser TM G and any combination thereof;
  • the non-essential amino acid is selected from glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, L-serine and combinations thereof;
  • the basic culture medium is selected from KO-DMEM, KO-DMEM/F12, ⁇ -MEM, DMEM, F12, MEM, BME, RPMI 1640, G-MEM and any combination thereof; preferably, the basic culture
  • the base is selected from KO-DMEM, KO-DMEM/F12, ⁇ -MEM, DMEM, DMEM/F12.
  • the serum substitute is KOSR, and selected from MSC serum-free additives (eg, TBD: catalog number SC2013-GB) and Ultraser TM G (eg, PALL: catalog number 15950-017) (hereinafter referred to as One of Ultroser G).
  • MSC serum-free additives eg, TBD: catalog number SC2013-GB
  • Ultraser TM G eg, PALL: catalog number 15950-017
  • the volume ratio of KOSR to MSC serum-free additive or Ultraser G is 2:1 to 150:1, for example, about 2:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about 10:1, about 20:1, about 50:1, about 80:1, about 100:1, about 120:1, or About 150:1.
  • the volume ratio of KOSR to MSC serum-free additive or Ultraser G is 10:1 to 1:2, such as about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, about 1:1 or about 1:2.
  • the content of KOSR is about 1-30% (v/v), about 1-20% (v/v), about 1-10% (v/v), about 2-10% ( v/v), or about 5-10% (v/v).
  • the content of MSC serum-free additive or Ultraser G is about 1-10% (v/v), or about 1-5% (v/v).
  • the second medium comprises: KO-DMEM/F12, ⁇ -MEM, MSC serum-free additive or Ultraser G, KOSR, glycine, L-alanine, L-asparagine, L -Aspartic acid, L-glutamic acid, L-proline, L-serine, L-alanyl-L-glutamine stabilized dipeptide, one or more growth factors (e.g. selected from One or more of VEGF, bFGF, EGF, TGF ⁇ , PDGF).
  • growth factors e.g. selected from One or more of VEGF, bFGF, EGF, TGF ⁇ , PDGF.
  • the second medium contains: 1-10% (v/v) Ultraser G, 1-20% (v/v) KOSR, 1-5 mM L-alanyl- A stabilized dipeptide of L-glutamine, one or more growth factors (for example, one or more selected from VEGF, bFGF, EGF, TGF ⁇ , and PDGF) each at a concentration of 1-100 ng/mL, And the following amino acids each at a concentration of 0.1-0.5 mM: glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, L-serine.
  • growth factors for example, one or more selected from VEGF, bFGF, EGF, TGF ⁇ , and PDGF
  • growth factors for example, one or more selected from VEGF, bFGF, EGF, TGF ⁇ , and PDGF
  • the following amino acids each at a concentration of 0.1-0.5 mM: gly
  • the second medium further comprises ascorbic acid.
  • the content of ascorbic acid is 1-100 ⁇ g/mL, for example, 1-100 ⁇ g/mL, 1-50 ⁇ g/mL, 1-20 ⁇ g/mL, or 5-20 ⁇ g/mL; for example, about 1 ⁇ g/mL, about 10 ⁇ g /mL, about 100 ⁇ g/mL, about 500 ⁇ g/mL, or about 1000 ⁇ g/mL.
  • the second medium consists essentially of the following components: KO-DMEM/F12, ⁇ -MEM, MSC serum-free additive or Ultraser G, KOSR, glycine, L-alanine, L-day Paraffin, L-aspartic acid, L-glutamic acid, L-proline, L-serine, L-alanyl-L-glutamine stabilized dipeptide, ascorbic acid, and one or more A growth factor (for example, one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF).
  • the second medium comprises: 1-5% (v/v) (e.g., about 1% (v/v), about 2% (v/v), about 3% (v/v) v), about 4% (v/v) or about 5% (v/v)) Ultraser G, 2-20% (v/v) (for example, about 2% (v/v), about 4% (v /v), about 6% (v/v), about 8% (v/v), about 10% (v/v), about 12% (v/v), about 14% (v/v), about 16% (v/v), about 18% (v/v) or about 20% (v/v)) KOSR, 1-5 mM L-alanyl-L-glutamine stabilized dipeptide, 1-1000 ⁇ g/mL ascorbic acid, one or more growth factors (e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) each at a concentration of 1-100 ng/mL,
  • growth factors
  • the second medium comprises: about 1% (v/v) Ultraser G, about 4% (v/v) KOSR, about 2 mM L-alanyl-L-gluten
  • the second medium comprises: about 1% (v/v) Ultraser G, about 6% (v/v) KOSR, about 2 mM L-alanyl-L-gluten
  • the second medium comprises: about 1% (v/v) Ultraser G, about 8% (v/v) KOSR, about 2 mM L-alanyl-L-gluten
  • the second medium comprises: about 2% (v/v) Ultraser G, about 4% (v/v) KOSR, about 1 mM L-alanyl-L-gluten
  • the second medium comprises: about 2% (v/v) Ultraser G, about 6% (v/v) KOSR, about 1 mM L-alanyl-L-gluten
  • the second medium comprises: about 2% (v/v) Ultraser G, about 8% (v/v) KOSR, about 1 mM L-alanyl-L-gluten
  • the second culture medium consists essentially of the following components: KO-DMEM/F12 (Gibco: catalog number 12660-012), ⁇ -MEM (HyClone: catalog number SH30265.01B), Ultraser G( PALL: article number 15950-017), KOSR (Thermo: article number 10828028), NEAA (Gibco: article number 11140050), GlutaMAX (Gibco: article number A1286001), ascorbic acid, one or more growth factors (for example selected from VEGF, bFGF, EGF) , TGF ⁇ , PDGF one or more).
  • the second medium comprises: 1-2% (v/v) Ultraser G, 4-6% (v/v) KOSR, 0.5-1.5% (v/v) ) GlutaMAX, 1-1000 ⁇ g/mL ascorbic acid, and one or more growth factors (e.g. selected from one or more of VEGF, bFGF, EGF, TGF ⁇ , PDGF) each at a concentration of about 1-100 ng/mL , And 1-2% (v/v) NEAA.
  • growth factors e.g. selected from one or more of VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the second medium comprises: about 1% (v/v) Ultraser G, about 4% (v/v) KOSR, about 1% (v/v) GlutaMAX , Ascorbic acid of about 100 ⁇ g/mL, one or more growth factors (e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) at a concentration of about 1-10 ng/mL, and about 1 %(V/v) NEAA.
  • growth factors e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the second medium comprises: about 1% (v/v) Ultraser G, about 6% (v/v) KOSR, about 1% (v/v) GlutaMAX , Ascorbic acid of about 100 ⁇ g/mL, one or more growth factors (e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) at a concentration of about 1-10 ng/mL, and about 1 %(V/v) NEAA.
  • growth factors e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the second medium comprises: about 1% (v/v) Ultraser G, about 8% (v/v) KOSR, about 1% (v/v) GlutaMAX , About 100 ⁇ g/mL ascorbic acid, one or more growth factors (for example, one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) at a concentration of about 1-10 ng/mL, and about 1 %(V/v) NEAA.
  • growth factors for example, one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the second medium comprises: about 2% (v/v) Ultraser G, about 4% (v/v) KOSR, about 0.5% (v/v) GlutaMAX , Ascorbic acid of about 100 ⁇ g/mL, one or more growth factors (e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) at a concentration of about 1-10 ng/mL, and about 1 %(V/v) NEAA.
  • growth factors e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the second medium comprises: about 2% (v/v) Ultraser G, about 6% (v/v) KOSR, about 0.5% (v/v) GlutaMAX , Ascorbic acid of about 100 ⁇ g/mL, one or more growth factors (e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) at a concentration of about 1-10 ng/mL, and about 1 %(V/v) NEAA.
  • growth factors e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the second culture medium comprises: about 2% (v/v) Ultraser G, about 8% (v/v) KOSR, about 0.5% (v/v) GlutaMAX , Ascorbic acid of about 100 ⁇ g/mL, one or more growth factors (e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF) at a concentration of about 1-10 ng/mL, and about 1 %(V/v) NEAA.
  • growth factors e.g., one or more selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF
  • the components contained in the first medium and the second medium are both cell therapy grade (CTS grade).
  • the basal medium such as KO-DMEM
  • serum replacement such as KOSR
  • the stabilized dipeptides are all cell therapy grade (CTS grade).
  • the step (1) includes culturing the pluripotent stem cells in a low-adsorption cell culture dish.
  • low-adsorption cell culture dish refers to a culture dish with a coating on the surface, which can prevent the adsorption of proteins on the surface of the culture dish, thereby minimizing the adhesion of the monolayer of cells to the culture container.
  • Such cell culture dishes are well known to those skilled in the art and include, but are not limited to, Corning's low-attachment culture dishes (Cat. No. 3262).
  • the duration of culture in step (1) is 3-14 days, for example, about 3 days, about 4 days, about 5 days, about 7 days, about 10 days, or about 14 days.
  • the duration of culture in the step (1) is 4-7 days, for example about 5 days.
  • the step (2) includes inoculating the embryoid bodies of step (1) into the culture vessel at a density of about 1 embryoid body/cm 2.
  • the step (2) includes culturing the plant in a petri dish coated with gelatin, type I collagen, type IV collagen, vitronectin, fibronectin or polylysine. The embryoid body.
  • the step (2) includes culturing the embryoid body in a petri dish coated with vitronectin.
  • the duration of culture in step (2) is 10-21 days, for example, about 10 days, about 14 days, or about 21 days.
  • the duration of culture in step (2) is 10-14 days, for example about 14 days.
  • the step (2) includes replacing freshness every day or every 1-7 days (for example, every 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days).
  • the second medium In some embodiments, the step (2) includes discarding every day or every 1-7 days (for example, every 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days)
  • the spent media (the spent media) is replaced with a fresh second media.
  • the culture conditions are 37°C and 5% CO 2 . In some embodiments, in steps (1)-(2), culture is performed in an incubator at 37° C. and 5% CO 2.
  • the cells attached to the culture container in the step (2) are mesenchymal stem cells of generation P0.
  • the confluence of the cells attached to the culture vessel described in step (2) is not less than about 80% (for example, not less than about 85%, not less than about 90%, or not less At about 95%), the cells can be separated from the culture vessel to obtain mesenchymal stem cells of generation P0.
  • the method further includes: (3) separating the cells attached to the culture container in step (2), so as to obtain mesenchymal stem cells.
  • the method further includes passage of the mesenchymal stem cells of step (3).
  • the cells are passaged .
  • the mesenchymal stem cells are passaged for 1, 2, 3, 4, or 5 passages.
  • the method of passage of cells is well known to those skilled in the art.
  • the method may include: separating the cells from the culture container and uniformly dispersing the cells in the culture medium, and then inoculating the culture container. Add an appropriate amount of medium, and replace an appropriate amount of fresh medium at intervals (for example, every 1 to 5 days) according to the cell growth state, and repeat the subculture operation when the cells grow to 70-100% confluence. Each time the cells are subcultured, the number of generations increases by 1.
  • the passaging includes a rate of about 5 ⁇ 10 3 -5 ⁇ 10 4 /cm 2 (e.g., about 5 ⁇ 10 3 /cm 2 , about 1 ⁇ 10 4 /cm 2 , about 2 ⁇ 10 4 /cm 2 , about 3 ⁇ 10 4 /cm 2 , about 4 ⁇ 10 4 /cm 2 , or about 5 ⁇ 10 4 /cm 2 ) for passage.
  • a rate of about 5 ⁇ 10 3 -5 ⁇ 10 4 /cm 2 e.g., about 5 ⁇ 10 3 /cm 2 , about 1 ⁇ 10 4 /cm 2 , about 2 ⁇ 10 4 /cm 2 , about 3 ⁇ 10 4 /cm 2 , about 4 ⁇ 10 4 /cm 2 , or about 5 ⁇ 10 4 /cm 2
  • a rate of about 5 ⁇ 10 3 -5 ⁇ 10 4 /cm 2 e.g., about 5 ⁇ 10 3 /cm 2 , about 1 ⁇ 10 4 /cm 2 ,
  • the passaging includes seeding cells in the second medium for culturing.
  • the separation includes disrupting the attachment of the mesenchymal stem cells to the culture vessel by: (i) contacting the culture with one or more enzymes selected from the group consisting of trypsin or Its analogs, collagenase, dispase, papain, a mixture of collagenase and dispase, and a mixture of collagenase and trypsin or its analogs; (ii) mechanical separation using cell scrapers, etc.; or, (iii) The culture is brought into contact with EDTA or EGTA.
  • one or more enzymes selected from the group consisting of trypsin or Its analogs, collagenase, dispase, papain, a mixture of collagenase and dispase, and a mixture of collagenase and trypsin or its analogs
  • the culture is brought into contact with EDTA or EGTA.
  • the separation includes disrupting the attachment of the mesenchymal stem cells to the culture vessel by enzymatic digestion.
  • the enzyme is trypsin (e.g., Gibco: Cat. No. 25200072).
  • the cell growth curve can be determined by the MTT method, WST method, DNA content detection method, ATP detection method, etc., to evaluate the growth activity of the umbilical cord mesenchymal stem cells.
  • the isolated and cultured umbilical cord mesenchymal stem cells can be identified by detecting cell surface markers by flow cytometry, three-way differentiation assay, and PCR method to detect cell expression genes.
  • any culture method known in the art can be used to propagate and maintain stem cells (for example, pluripotent stem cells or pluripotent stem cells, such as embryonic stem cells, haploid stem cells, induced pluripotent stem cells, or adult stem cells).
  • embryonic stem cells can be cultured in the presence of feeder cells such as murine cells (e.g., murine embryonic fibroblasts (MEF)), human feeder cells (e.g., adult skin cells, neonatal dermal fibroblasts (HNDF), etc.).
  • feeder cells such as murine cells (e.g., murine embryonic fibroblasts (MEF)), human feeder cells (e.g., adult skin cells, neonatal dermal fibroblasts (HNDF), etc.
  • embryonic stem cells can be cultured in cultures free of foreign substances, and/or under feeder-free conditions.
  • embryonic stem cells can be cultured on a matrix that can be selected from: laminin, fibronectin, vitronectin, proteoglycan, nestin, collagen, collagen I, collagen IV, collagen VIII, Heparan sulfate, Matrigel (TM) (a soluble preparation from Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells), CellStart, human basement membrane extract, and any combination thereof.
  • a matrix can be selected from: laminin, fibronectin, vitronectin, proteoglycan, nestin, collagen, collagen I, collagen IV, collagen VIII, Heparan sulfate, Matrigel (TM) (a soluble preparation from Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells), CellStart, human basement membrane extract, and any combination thereof.
  • the present invention also relates to a population of mesenchymal stem cells produced by the method described in the second aspect.
  • the mesenchymal stem cell population is as defined in the first aspect.
  • the present invention provides a kit comprising a first medium and a second medium provided separately, wherein:
  • the first medium is a basic medium added with the following substances: one or more serum substitutes, one or more non-essential amino acids, glutamine or L-alanyl-L-glutamine stabilization Dipeptide, and bFGF;
  • the second medium is a basic medium added with the following substances: one or more serum substitutes, one or more non-essential amino acids, glutamine or L-alanyl-L-glutamine stabilization Dipeptide, and one or more growth factors.
  • the first medium and the second medium are as defined in any of the embodiments of the second aspect.
  • the present invention provides a culture comprising the mesenchymal stem cell population according to the first or third aspect, and a culture medium.
  • the medium is any medium that can be used for stem cell culture, such as KO-DMEM, KO-DMEM/F12 (equivalent mixture of KO-DMEM and F-12), ⁇ -MEM, DMEM/F-12 (DMEM And F-12 (equal mixed liquid), DMEM, IMDM, F-12, RPMI1640, and a mixed medium formed by combining any of the above.
  • the above-mentioned culture medium optionally further contains supplementary substances, such as serum (e.g., fetal bovine serum, human serum, goat serum, etc.), serum substitutes (e.g., KOSR, etc.), bovine serum albumin (BSA), antibiotics, vitamins, Minerals.
  • serum e.g., fetal bovine serum, human serum, goat serum, etc.
  • serum substitutes e.g., KOSR, etc.
  • BSA bovine serum albumin
  • the medium is the second medium as defined in any of the embodiments of the second aspect.
  • the culture of the present invention can be formulated and administered as a pharmaceutical composition.
  • a pharmaceutical composition may be in any form known in the medical field, and is preferably an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • sterile isotonic aqueous or non-aqueous solution e.g., balanced salt solution or physiological saline
  • dispersion suspension or emulsion.
  • the present invention provides a culture supernatant, which is the supernatant of the culture described in the fifth aspect; or, is the culture medium described in the first or third aspect.
  • the culture supernatant produced by the mass of stem cells.
  • the medium is the second medium as defined in any of the embodiments of the second aspect.
  • the culture supernatant does not contain the mesenchymal stem cell population.
  • the culture supernatant of the present invention can be formulated and administered as a pharmaceutical composition.
  • Such pharmaceutical compositions can be in any form known in the medical field, such as tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (Including injection, lyophilized powder) and other forms.
  • the present invention also relates to a method for preparing the culture supernatant as described herein, which comprises the following steps:
  • step (2) Collect the supernatant of the culture obtained in step (1) (that is, the culture supernatant).
  • the method further includes: (3) processing the supernatant obtained in step (2), and the processing is selected from the group consisting of centrifugation, concentration, solvent replacement, dialysis, freezing, drying, and freeze drying , Dilution, desalination, preservation, and any combination thereof.
  • the mesenchymal stem cell population of the present invention can be cultured using any medium and culture conditions known in the art that can be used for stem cell culture.
  • the mesenchymal stem cell population is cultured using the second medium defined in any one of the embodiments of the second aspect.
  • the culture supernatant of the present invention does not contain serum to improve safety. Therefore, in certain exemplary embodiments, in step (1), the mesenchymal stem cell population may be cultured using a serum-free medium (for example, a basal medium or a serum-free medium), thereby Obtain serum-free culture supernatant.
  • a serum-free medium for example, a basal medium or a serum-free medium
  • the serum-free medium may be used for culture during the entire culture process, or in the last or last few subcultures.
  • the culture supernatant obtained in step (2) may be subjected to dialysis or solvent replacement to remove serum, thereby also obtaining a serum-free culture supernatant.
  • the present invention also relates to a method for culturing the mesenchymal stem cell population according to the first or third aspect, which includes the use of microcarriers.
  • the microcarriers include carrier sheets (such as TableTrix), carrier balls (such as CultiSpher, Coring, Cytodex 1, 2, 3, Solohill, Cytopore, Cytoline), etc., or liquid microcarriers, large Porous gelatin microcarriers, polystyrene microcarriers, PHEMA microcarriers, chitin microcarriers, polyurethane foam microcarriers, alginate gel microcarriers, magnetic microcarriers, etc.
  • carrier sheets such as TableTrix
  • carrier balls such as CultiSpher, Coring, Cytodex 1, 2, 3, Solohill, Cytopore, Cytoline
  • liquid microcarriers large Porous gelatin microcarriers, polystyrene microcarriers, PHEMA microcarriers, chitin microcarrier
  • the microcarriers of the present invention can improve the survival rate of the mesenchymal stem cell population after cryopreservation.
  • the mesenchymal stem cell population and/or the mesenchymal stem cell population cultured on microcarriers are cryopreserved for at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days After days, 8 days, 9 days, 10 days, 1 month, 2 months, 3 months, half a year, one year later, it can be in the range of 37°C ⁇ 3°C, 37°C ⁇ 2°C, or 37°C ⁇ 1°C Internal recovery is at least 50%, 60%, 70%, 80%, 90% survival rate.
  • the microcarrier comprises a material selected from, consists of a material selected from the following, or consists essentially of a material selected from the following: protein, cellulose, polyethylene, polystyrene, glass , Dextran, diethylaminoethanol (DEAE)-dextran, collagen, collagen-gylcose-aminoglycan, gelatin, acrylamide (e.g. polyacrylamide), and any combination thereof.
  • a material selected from consists of a material selected from the following, or consists essentially of a material selected from the following: protein, cellulose, polyethylene, polystyrene, glass , Dextran, diethylaminoethanol (DEAE)-dextran, collagen, collagen-gylcose-aminoglycan, gelatin, acrylamide (e.g. polyacrylamide), and any combination thereof.
  • the microcarrier does not have a matrix coating. In some embodiments, the surface of the microcarrier is coated with a matrix.
  • the matrix includes an extracellular matrix.
  • the matrix includes Matrigel TM (BD Biosciences), hyaluronic acid, laminin, fibronectin, vitronectin, collagen, elastin, heparan sulfate, dextran, dextran sulfate One or more of sugar and chondroitin sulfate.
  • the microcarrier is a non-porous microcarrier. In certain embodiments, the microcarrier is a porous microcarrier.
  • the microcarrier culture is performed under static culture conditions.
  • the microcarrier culture is performed under dynamic culture conditions.
  • the culture method includes: microcarrier culture of the mesenchymal stem cell population in a culture medium, and the growth medium is a basic culture medium containing: one or more serums Alternatives, one or more non-essential amino acids, stabilized dipeptides of glutamine or L-alanyl-L-glutamine, and one or more growth factors.
  • the growth medium is defined as the second medium described in any of the embodiments of the second aspect.
  • the present invention provides a pharmaceutical composition comprising at least one or more selected from the following: the mesenchymal stem cell population of the first aspect or the third aspect, and the mesenchymal stem cell population of the fifth aspect The culture supernatant of the sixth aspect.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient, or other auxiliary materials that may be required.
  • the term "adjuvant” refers to substances other than the main drug that are necessary in the preparation or compounding process of a pharmaceutical preparation. It is generally required that these substances have no physiological activity and do not affect the efficacy, content determination and stability of the drug in the drug preparation.
  • the main purpose of adding excipients is to facilitate the preparation and clinical application of the preparation.
  • the excipients used in the pharmaceutical composition of the present invention are medicinal and are also compatible with the active ingredient.
  • the pharmaceutical composition comprises a therapeutically effective amount of the mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of the culture supernatant as described herein.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen (e.g., collagen gel, collagen scaffold, gelatin microcarrier), gelatin (e.g., gelatin gel, gelatin electrospun Silk, gelatin scaffolds, gelatin microcarriers, etc.), aminated gelatin (such as aminated gelatin gel, aminated gelatin electrospinning, aminated gelatin scaffold, aminated gelatin microcarrier, etc.), chitosan (such as chitosan) Gel, chitosan scaffold, etc.), decellularized scaffold (such as uterine decellularized scaffold, heart decellularized scaffold, etc.), skin repair membrane, bone repair membrane, oral repair membrane, cellulose, fibrin, polylactic acid, cellulose Polylactic acid, polyurethane, tropoelastin, hyaluronic acid, sodium alginate, polyethylene oxide, polyethylene glycol, polylactic acid glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix Or any combination
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including an injection solution, a lyophilized powder) or an aerosol.
  • the drug combination is a propellant, which can be used for skin surface repair or transplantation.
  • the pharmaceutical composition may be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Cell Therapy Stem Cell Transplantation, Gene Therapy and Cellular Immunotherapy
  • G. Morstyn and W. Sheridan Cell Therapy: Stem Cell
  • Transplantation, Gene Therapy, and Cellular Immunotherapy Cambridge University Press, 1996
  • Hematopoietic Stem Cell Therapy EDBall, J. Lister & P. Law, Churchill Livingstone, 2000.
  • the pharmaceutical composition comprises injections (including physiological saline, lactated Ringer's solution, compound electrolyte injection, 5% glucose injection, 20% HSA injection, succinyl gelatin injection, succinyl Gelatin MIX Injection, MZJ Injection 1, MZJ Injection 2, MZJ Injection 3, Human Serum Protein Injection, Bomari A, Potassium Chloride Injection, Magnesium Sulfate Injection, Sodium Bicarbonate Injection, Glucose Chloride Sodium Injection, Compound Sodium Chloride Injection (Ringer's Solution), Dextran 20 Glucose Injection (Small Molecule), Amino Acid Injection, Hydroxyethyl Starch 40 Sodium Chloride Injection, Hydroxyethyl Starch 40 Chloride Sodium injection, hydroxyethyl starch 40 sodium chloride injection, low molecular weight heparin calcium for injection, heparin sodium injection, coenzyme A for injection, disodium
  • the injection of the drug combination is not cryopreserved or after cryopreservation
  • the cells can be stored on 14 days, 13 days, 12 days, 11 days, 10 days, 9 days, 8 days, 7 days, and 6 days. , 5 days, 4 days, 3 days, 2 days, 1 day, maintain the survival rate of the pharmaceutical composition at least 50%, 60%, 70%, 80%, 90% at about 4°C.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials (such as but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid.)
  • pharmaceutically acceptable biological materials such as but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid.
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution e.g., balanced salt solution or physiological saline
  • dispersion suspension or emulsion.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including an injection solution, a lyophilized powder) or an aerosol.
  • the pharmaceutical composition is an injection, such as a solution injection.
  • the injection contains one or more injection additives, for example selected from the group consisting of solubilizers, wetting agents, emulsifiers, buffers, suspending agents, chelating agents, antioxidants, and bacteriostatic agents , Local anesthetics, isotonic regulators, fillers, protective agents and any combination thereof.
  • injection additives for example selected from the group consisting of solubilizers, wetting agents, emulsifiers, buffers, suspending agents, chelating agents, antioxidants, and bacteriostatic agents , Local anesthetics, isotonic regulators, fillers, protective agents and any combination thereof.
  • the injection contains an isotonic or hypertonic solution; preferably, the solution is selected from NaCl injection (for example, 0.9% to 2.7% NaCl injection), glucose injection (for example, 4% to 4%). 5% glucose injection), sodium lactate Ringer injection, compound electrolyte injection, HSA injection (for example, 10%-20% HSA injection), succinyl gelatin injection (for example, 4% to 5% succinyl gelatin injection) ) And any combination thereof.
  • NaCl injection for example, 0.9% to 2.7% NaCl injection
  • glucose injection for example, 4% to 4%
  • 5% glucose injection for example, sodium lactate Ringer injection
  • compound electrolyte injection for example, HSA injection (for example, 10%-20% HSA injection), succinyl gelatin injection (for example, 4% to 5% succinyl gelatin injection)
  • HSA injection for example, 10%-20% HSA injection
  • succinyl gelatin injection for example, 4% to 5% succinyl gelatin injection
  • the dosage of the mesenchymal stem cells is not less than 1 ⁇ 10 4 cells/mL (for example, not less than 1 ⁇ 10 4 cells/ml, not less than 3 ⁇ 10 4 cells/ml , Not less than 5 ⁇ 10 4 pieces/ml, not less than 7 ⁇ 10 4 pieces/ml, not less than 1 ⁇ 10 5 pieces/ml, not less than 3 ⁇ 10 5 pieces/ml, not less than 5 ⁇ 10 5 pieces/ml, not less than 7 ⁇ 10 5 pieces/ml, not less than 1 ⁇ 10 6 pieces/ml, not less than 3 ⁇ 10 6 pieces/ml, not less than 5 ⁇ 10 6 pieces/ml, Not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml, not less than 7 ⁇ 10 7 pcs/ml, not less than 1 ⁇ 10 8 pcs/ml, not less than 3 ⁇ 10 8 pcs/ml, not
  • the dosage of the mesenchymal stem cells is not less than 1 ⁇ 10 3 cells/kg (for example, not less than 1 ⁇ 10 3 cells/kg, not less than 3 ⁇ 10 3 cells/kg , Not less than 5 ⁇ 10 3 pcs/kg, not less than 7 ⁇ 10 3 pcs/kg, not less than 1 ⁇ 10 4 pcs/kg, not less than 3 ⁇ 10 4 pcs/kg, not less than 5 ⁇ 10 4 pcs/kg, not less than 7 ⁇ 10 4 pcs/kg, not less than 1 ⁇ 10 5 pcs/kg, not less than 3 ⁇ 10 5 pcs/kg, not less than 5 ⁇ 10 5 pcs/kg, Not less than 7 ⁇ 10 5 /kg, not less than 1 ⁇ 10 6 /kg, not less than 3 ⁇ 10 6 /kg, not less than 5 ⁇ 10 6 /kg, not less than 7 ⁇ 10 6 pieces/kg, not less than 1 ⁇ 10 7 pieces/kg, not less than 3 ⁇ 10 7 pieces/kg/
  • the dose administered is not less than 1 ⁇ 10 4 /time (for example, not less than 1 ⁇ 10 4 /time, not less than 3 ⁇ 10 4 /time, not less than 5 ⁇ 10 4 /time, not less than 7 ⁇ 10 4 /time, not less than 1 ⁇ 10 5 /time, not less than 3 ⁇ 10 5 /time, not less than 5 ⁇ 10 5 /time, Not less than 7 ⁇ 10 5 /time, not less than 1 ⁇ 10 6 /time, not less than 3 ⁇ 10 6 /time, not less than 5 ⁇ 10 6 /time, not less than 7 ⁇ 10 6 /time, not less than 1 ⁇ 10 7 /time, not less than 3 ⁇ 10 7 /time, not less than 5 ⁇ 10 7 /time, not less than 7 ⁇ 10 7 /time, no Less than 1 ⁇ 10 8 /time, not less than 3 ⁇ 10 8 /time, not less than 5 ⁇ 10 8 /time, not less than 7 ⁇ 10 8 /time, not less than 1 ⁇ 10 9 Number/time,
  • the injection also contains the following functional ingredients:
  • the functional ingredient is selected from serum substitutes, non-essential amino acids, glutamine, stabilized dipeptides of L-alanyl-L-glutamine, growth factors, and any combination thereof.
  • the functional ingredient is selected from KOSR, MSC serum-free additives, Ultraser TM G, glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamine Acid, L-proline, L-serine, VEGF, bFGF, EGF, TGF ⁇ , PDGF and any combination thereof.
  • the drug combination is a propellant, which can be used for skin surface repair or transplantation.
  • the pharmaceutical composition may be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Cell Therapy Stem Cell Transplantation, Gene Therapy and Cellular Immunotherapy
  • G. Morstyn and W. Sheridan Cell Therapy: Stem Cell
  • Transplantation, Gene Therapy, and Cellular Immunotherapy Cambridge University Press, 1996
  • Hematopoietic Stem Cell Therapy EDBall, J. Lister & P. Law, Churchill Livingstone, 2000.
  • the pharmaceutical composition comprises injections (including physiological saline, lactated Ringer's solution, compound electrolyte injection, 5% glucose injection, 20% HSA injection, succinyl gelatin injection, succinyl Gelatin MIX Injection, MZJ Injection 1, MZJ Injection 2, MZJ Injection 3, Human Serum Protein Injection, Bomari A, Potassium Chloride Injection, Magnesium Sulfate Injection, Sodium Bicarbonate Injection, Glucose Chloride Sodium Injection, Compound Sodium Chloride Injection (Ringer's Solution), Dextran 20 Glucose Injection (Small Molecule), Amino Acid Injection, Hydroxyethyl Starch 40 Sodium Chloride Injection, Hydroxyethyl Starch 40 Chloride Sodium injection, hydroxyethyl starch 40 sodium chloride injection, low molecular weight heparin calcium for injection, heparin sodium injection, coenzyme A for injection, disodium
  • the injection of the drug combination is not cryopreserved or after cryopreservation
  • the cells can be stored on 14 days, 13 days, 12 days, 11 days, 10 days, 9 days, 8 days, 7 days, and 6 days. , 5 days, 4 days, 3 days, 2 days, 1 day, maintain the survival rate of the pharmaceutical composition at least 50%, 60%, 70%, 80%, 90% at about 4°C.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials (such as but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid.)
  • pharmaceutically acceptable biological materials such as but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid.
  • the present invention provides a product comprising a mesenchymal stem cell population and a biological scaffold, the average MMP1 expression level of the mesenchymal stem cell population is at least about 10 times that of primary mesenchymal stem cells; and/or The average PGE2 expression level of the mesenchymal stem cell population is at least about 10 times that of the primary mesenchymal stem cells.
  • the present invention provides a product comprising a mesenchymal stem cell population and a biological scaffold, the average MMP1 expression level of the mesenchymal stem cell population is at least about 10 times that of primary mesenchymal stem cells; optionally Specifically, the average PGE2 expression level of the mesenchymal stem cell population is at least about 10 times that of the primary mesenchymal stem cells.
  • the population of mesenchymal stem cells is produced in vitro.
  • the mesenchymal stem cell population is as defined or described above.
  • the population of mesenchymal stem cells is partially or fully supported on the bioscaffold.
  • the material used to prepare the bioscaffold is degradable or non-degradable.
  • the materials used to prepare the bioscaffold are naturally occurring, artificially synthesized, recombinantly produced, modified, or any combination thereof.
  • the naturally occurring material is selected from collagen (e.g. type I, type II, type III collagen), fibrin, silk protein, cellulose, chitosan, alginate (e.g. seaweed Sodium), starch, hyaluronic acid, laminin, elastin, agarose, gelatin, dextran, extracellular matrix, silicate, or any combination thereof.
  • the artificially synthesized material is selected from polyphosphazene, polyacrylic acid and its derivatives (for example, polymethacrylic acid, copolymer of acrylic acid and methacrylic acid), polylactic acid (PLA), polyhydroxyl Acetic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), polyorthoester (POE), polycaprolactone (PCL), polyhydroxybutyrate (PHB), polyamino acid (such as polylysine) , Polyurethane, polyethylene oxide, polyethylene glycol, polylactic acid glycolic acid, silicone rubber, acellular scaffold or any combination thereof.
  • polyacrylic acid and its derivatives for example, polymethacrylic acid, copolymer of acrylic acid and methacrylic acid
  • PLA polylactic acid
  • PGA polyhydroxyl Acetic acid
  • PLGA polylactic acid-glycolic acid copolymer
  • POE polyorthoester
  • PCL polycaprolactone
  • PHB polyhydroxybutyrate
  • the modified material is selected from modified alginate, modified gelatin or a combination thereof, preferably, the modified alginate is oxidized alginate (Such as oxidized sodium alginate), preferably, the modified gelatin is aminated gelatin.
  • the material used to prepare the bioscaffold is selected from collagen, aminated gelatin, chitosan, or any combination thereof.
  • the biological scaffold is solid or semi-solid (such as a gel).
  • the biological scaffold has a layered structure (e.g., single-layer, double-layer or multi-layer, such as biofilm, skin repair film), or a sheet-like structure (e.g., rectangle, square, circle, ellipse). Shape, hexagonal or irregularly shaped sheet structure), or hollow tubular structure, or hollow ring (such as torus), or hollow three-dimensional structure (such as hollow cube, hollow sphere, hollow rectangular prism, hollow cylinder Body, or a hollow, irregular-shaped three-dimensional structure), or a solid three-dimensional structure (such as a solid cube, a solid sphere, a solid rectangular prism, a solid cylinder, or a solid irregular-shaped three-dimensional structure), or any combination thereof.
  • a layered structure e.g., single-layer, double-layer or multi-layer, such as biofilm, skin repair film
  • a sheet-like structure e.g., rectangle, square, circle, ellipse.
  • Shape, hexagonal or irregularly shaped sheet structure
  • the biological scaffold mimics the shape of natural tissues or organs.
  • the biological scaffold has a sheet-like structure, a layered structure, or a hollow ring (such as a circular ring) structure.
  • the biological scaffold is selected from a collagen scaffold, a skin repair membrane, a gelatin scaffold, an aminated gelatin scaffold, and a chitosan scaffold.
  • the bioscaffold has a load of not less than 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 pieces/ml, and not less than 1 ⁇ 10 4 pieces/ml.
  • the article further contains other active ingredients.
  • the other active ingredients are partially or fully supported on the bioscaffold.
  • the other active ingredients are selected from drugs for treating osteoarthropathy (such as meniscus injury, bone injury), drugs for treating heart disease (such as myocardial infarction), and treatment for neurological diseases (such as spinal cord injury).
  • drugs for treating osteoarthropathy such as meniscus injury, bone injury
  • drugs for treating heart disease such as myocardial infarction
  • neurological diseases such as spinal cord injury
  • drugs for treating skin diseases such as skin damage, burns, scalds
  • drugs for treating eye diseases such as corneal alkali burns
  • the drug for treating osteoarthritis is selected from the group consisting of glucosamine sulfate capsules, chondroitin sulfate, sodium hyaluronate injection, anti-bone hyperplasia tablets, osteopeptide tablets, Henggu bone wound healing agent, root Tongping granules, non-steroidal anti-inflammatory drugs (such as loxoprofen sodium tablets, diclofenac sodium sustained-release tablets, celecoxib, meloxicam, indomethacin tablets, Voltaren ointment) or any combination thereof.
  • non-steroidal anti-inflammatory drugs such as loxoprofen sodium tablets, diclofenac sodium sustained-release tablets, celecoxib, meloxicam, indomethacin tablets, Voltaren ointment
  • the drug for treating heart disease is selected from aspirin, clopidogrel, ticagrelor, ACE1, ARBs, ⁇ -blockers, calcium antagonists, nitrate vasodilators Agent, trimetazidine hydrochloride, nicorandil, lidocaine, amiodarone, quinidine, or any combination thereof.
  • the drug for treating neurological diseases is selected from the group consisting of carbamazepine, phenobarbital, phenytoin, sodium valproate, clonazepam, lamotrigine, oxcarbazepine, donepezil, Memantine, vitamin B1, methylcobalamin, vaccinia vaccination rabbit inflammatory skin extract, alteplase, aspirin, clopidogrel, low molecular weight heparin, edaravone, ureclin, butylphthalide, injection Use gamma globulin, brompistigmine, glucocorticoids or any combination thereof.
  • the drug for treating skin diseases is selected from the group consisting of ebastine tablets, loratadine tablets, cetirizine tablets, mometasone furoate ointment, halometasone ointment, mupirocin ointment, Fusidic acid ointment, cefixime tablets, roxithromycin tablets, netifene ketoconazole ointment, sertaconazole ointment, itraconazole tablets, terbinafine tablets, acyclovir tablets, Cyclovir tablets, penciclovir ointment, interferon gel, or any combination thereof.
  • the drug for treating eye diseases is an antibacterial and anti-inflammatory drug.
  • the product further comprises ingredients for culturing/differentiating cells.
  • the components of the cultured/differentiated cells are selected from serum substitutes, non-essential amino acids, glutamine or stabilized dipeptides of L-alanyl-L-glutamine, growth factors, or Any combination of it.
  • the serum replacement is selected from KOSR, MSC serum-free additives, Ultraser TM G, or any combination thereof.
  • the non-essential amino acid is selected from glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, L-serine Or any combination thereof.
  • the growth factor is selected from VEGF, bFGF, EGF, TGF ⁇ , PDGF, or any combination thereof.
  • the present invention provides the use of the aforementioned product in the preparation of a medicament for the treatment and/or prevention of osteoarthropathy (such as meniscus injury, bone injury), heart disease (such as myocardial injury) in a subject. Infarction), neurological disease (such as spinal cord injury), skin disease (such as skin injury, burn, scald), eye disease (such as corneal alkali burn), or any combination thereof.
  • osteoarthropathy such as meniscus injury, bone injury
  • heart disease such as myocardial injury
  • neurological disease such as spinal cord injury
  • skin disease such as skin injury, burn, scald
  • eye disease such as corneal alkali burn
  • the medicament is used to treat and/or prevent spinal cord injury, skin injury, corneal alkali burn, or any combination thereof in a subject.
  • the present invention provides a method for treating and/or preventing diseases in a subject, which comprises administering (such as implanting or sticking, preferably implanting) the aforementioned product to a subject in need thereof,
  • the disease is selected from osteoarthropathy (e.g. meniscus injury, bone injury), heart disease (e.g. myocardial infarction), nervous system disease (e.g. spinal cord injury), skin disease (e.g. skin injury, burn, scald), eye disease (Such as corneal alkali burn) or any combination thereof.
  • the disease is selected from spinal cord injury, skin injury, corneal alkali burn, or any combination thereof.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of diseases in a subject, or in preparation Use in a medicine for preventing and/or treating diseases in a subject, and a method for preventing and/or treating diseases in a subject, which comprises administering the intermediary of the present invention to a subject in need thereof Mesenchymal stem cell population, culture, culture supernatant, or the pharmaceutical composition of the present invention.
  • the subject is a mammal, such as a human.
  • the disease is selected from osteoarthropathy (e.g., meniscus injury, osteoarthritis, or bone injury, etc.), reproductive system disease (e.g., ovarian aging, ovarian insufficiency, endometrial injury, etc.) Uterine trauma, intrauterine adhesions, or thin uterus, etc.), heart disease (for example, myocardial infarction, etc.), lung disease (for example, idiopathic pulmonary fibrosis, acute respiratory distress, pneumoconiosis, or pneumonia, etc.), skin disease (E.g., psoriasis, skin injuries, bedsores, pressure sores, or burns, etc.), eye diseases (e.g., corneal injury, etc.), neurological diseases (e.g., spinal cord injury, cerebral palsy, stroke, Alzheimer’s disease , Alzheimer’s, or neuropathic pain, etc.), digestive system diseases (e.g., inflammatory bowel disease, colitis, Crohn’s
  • the mesenchymal stem cell population or culture as described herein, or the pharmaceutical composition containing the mesenchymal stem cell population or culture may be administered to the subject in various suitable ways.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • Those skilled in the art know how to select a suitable cell transplantation route according to the location and nature of the lesion.
  • the pharmaceutical composition comprises a therapeutically effective amount of a culture supernatant as described herein.
  • the culture supernatant of the present invention can be formulated and administered as a medicine.
  • Such a pharmaceutical composition may contain a therapeutically effective amount of the culture supernatant.
  • the culture supernatant of the present invention or a pharmaceutical composition containing the culture supernatant can be administered to a subject in various suitable ways.
  • the culture supernatant of the present invention, or a pharmaceutical composition comprising the culture supernatant can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for the prevention, treatment, delay and/or alleviation of female reproductive system diseases; or, the present invention provides The method for preventing, treating, delaying and/or alleviating female reproductive system diseases includes administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the female reproductive system diseases include: (1) gynecological inflammations, such as vulvitis, vaginitis, cervicitis, endometritis, uterine inflammatory disease, pelvic inflammatory disease, adnexitis; (2) ) Gynecological tumors, such as benign tumors and malignant tumors; (3) Menstrual disorders, such as dysmenorrhea, increased menstrual flow, and decreased menstrual flow; (4) Infertility, such as infertility caused by ovulation dysfunction, and infertility caused by blocked fallopian tubes Pregnancy, immune infertility.
  • the female reproductive system disease is selected from the group consisting of ovarian aging, ovarian insufficiency, endometrial injury, uterine trauma, intrauterine adhesions, and thin uterus.
  • the endometrial injury is mainly the injury of the basal layer of the endometrium, which is manifested as irregular menstrual cycle, or the amount of menstrual bleeding is small, and the menstrual bleeding time is shortened.
  • most endometrial injuries occur after abortion, including artificial abortion or medical abortion.
  • related intrauterine operations may also cause damage to the endometrium.
  • endometritis is inflammation of the endometrium. According to the length of the disease, it can be divided into acute endometritis and chronic endometritis.
  • uterine adhesions are a type of uterine disease in female reproductive system diseases, which refers to endometrial damage caused by various reasons, including trauma to the uterus of pregnancy and non-pregnancy, leading to endometrial
  • the basal layer is damaged, so that the uterine cavity and/or cervical canal is partially or completely occluded, and the uterine wall adheres to each other, resulting in abnormal menstruation, infertility or recurrent miscarriage, etc. There are usually no typical symptoms. Its essence is endometrial fibrosis.
  • endometrial lesions Such as: endometrial lesions, foreign bodies in the uterine cavity, benign endometrial lesions, uterine malformations, endometrial malignant lesions, etc.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from estrogen, anti-estrogens or selective estrogen receptor modulators, androgens, anti-androgens or progestins.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 pieces/ml, not less than 5 ⁇ 10 4 pieces/ml, not less than 7 ⁇ 10 4 pieces/ml, not less than 1 ⁇ 10 5 pieces/ml, not less than 3 ⁇ 10 5 pieces/ ml, not less than 5 ⁇ 10 5 pcs/ml, not less than 7 ⁇ 10 5 pcs/ml, not less than 1 ⁇ 10 6 pcs/ml, not less than 3 ⁇ 10 6 pcs/ml, not less than 5 ⁇ 10 6 pieces/ml, not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml , Not less than 7 ⁇ 10 7 pieces/ml, not less than 1 ⁇ 10 8 pieces/m
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the present invention also provides a product for preventing, treating, delaying and/or alleviating female reproductive system diseases, which contains the mesenchymal stem cell population of the present invention.
  • the product further contains an additional active ingredient, and the additional active ingredient is as defined above.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the product is an injection, microinjection, mucosal patch, enema, suppository, gel, oral, aerosol, drop, ointment, embedding or capsule, preferably For injections.
  • the product is an implant.
  • Uterine adhesions including endometrial fibrosis due to endometrial injury, partial or complete occlusion of the uterine cavity, which then leads to oligomenorrhea, amenorrhea, infertility or repeated miscarriage, etc.
  • endometrial fibrosis due to endometrial injury, partial or complete occlusion of the uterine cavity, which then leads to oligomenorrhea, amenorrhea, infertility or repeated miscarriage, etc.
  • the incidence and detection rate of intrauterine adhesions have gradually increased, and the age of onset is showing a younger trend, which has become the second leading cause of secondary infertility in women.
  • the treatment steps are hysteroscopic hysteroscopy and intrauterine placement.
  • IUDs and postoperative application of estrogen and progesterone but there are problems such as long treatment cycle, low cure rate, easy recurrence of adhesions, low pregnancy rate, high-dose estrogen application increases the risk of breast and endometrial tumors in patients, and serious muscularity Or the basal layer of the endometrium in the connective tissue has been destroyed, and the response to estrogen and progesterone is poor.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for preventing, treating, delaying and/or reducing intrauterine adhesions; or, the present invention provides prevention , A method for treating, delaying and/or alleviating intrauterine adhesions, which comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the mesenchymal stem cell population of the present invention can thicken the endometrium, increase blood vessels, glands and cells, improve uterine cavity adhesion, restore uterine cavity shape and/or reduce uterine effusion.
  • the mesenchymal stem cell population of the present invention can prevent or treat the symptoms of uterine adhesions, such as reducing the increase in intrauterine fluid accumulation.
  • the intrauterine adhesions include uterine adhesions in infertile persons or uterine adhesions caused by abortion.
  • the mesenchymal stem cell population of the present invention can improve uterine morphology and inhibit intrauterine adhesions.
  • the mesenchymal stem cell population of the present invention can promote endometrial repair and regeneration, for example, repair and regeneration of damaged endometrium, so as to enhance the ability to reproduce offspring.
  • the mesenchymal stem cell population of the present invention can restore uterine scars to prevent or treat intrauterine adhesions.
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the medicament comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension, or emulsion.
  • a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution e.g., balanced salt solution or physiological saline
  • dispersion suspension, or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid, etc.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from estrogen, anti-estrogens or selective estrogen receptor modulators, androgens, anti-androgens or progestins.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 pieces/ml, not less than 5 ⁇ 10 4 pieces/ml, not less than 7 ⁇ 10 4 pieces/ml, not less than 1 ⁇ 10 5 pieces/ml, not less than 3 ⁇ 10 5 pieces/ ml, not less than 5 ⁇ 10 5 pcs/ml, not less than 7 ⁇ 10 5 pcs/ml, not less than 1 ⁇ 10 6 pcs/ml, not less than 3 ⁇ 10 6 pcs/ml, not less than 5 ⁇ 10 6 pieces/ml, not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml , Not less than 7 ⁇ 10 7 pieces/ml, not less than 1 ⁇ 10 8 pieces/m
  • POI Primary ovarian insufficiency
  • Amenorrhea/oligomenorrhea for at least 4 months; (2) 2 blood FSH>25U/L (monitoring time separated by at least 4 weeks). It is characterized by menstrual disorders (amenorrhea or oligomenorrhea), elevated gonadotropins, and low estrogen (hot flashes and sweating, facial flushing, low libido, etc.).
  • the incidence of POI is about 1%, and the incidence of different races is slightly different.
  • the incidence of POI in patients with primary amenorrhea is 10%-28%, and the incidence of POI in patients with secondary amenorrhea is 4%-18%.
  • POI causes of POI include heredity, immunity, iatrogenic (radiochemotherapy, immunosuppressive therapy, surgical treatment, etc.), but most of the causes of POI are unknown. POI may be related to a variety of endocrine diseases, including hypoparathyroidism and hypoadrenaline. Pelvic surgery may also result in impaired ovarian function. Approximately 4% of POI patients have adrenal or ovarian antibodies, indicating that this disease is autoimmune. In many cases, the mechanism is unclear. POI can cause the loss of female fertility and increase the risk of osteoporosis, lipid metabolism and cardiovascular disease. Early amenorrhea during the reproductive period and loss of fertility will increase the psychological burden of women and reduce the quality of married life, resulting in a series of serious psychological and social problems.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for preventing, treating, delaying and/or reducing ovarian insufficiency (such as primary ovarian function). Insufficiency); Or, the present invention provides a method for preventing, treating, delaying and/or reducing ovarian insufficiency (such as primary ovarian insufficiency), which includes administering a preventive and/or therapeutically effective amount to a subject in need The mesenchymal stem cell population or its culture supernatant.
  • the mesenchymal stem cell population of the present invention can improve blood sex hormones (such as FSH and E2) levels, increase the number of follicles, improve body weight and ovarian weight, restore ovulation levels, and/or improve fertility levels.
  • blood sex hormones such as FSH and E2
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain embodiments, administration is via abdominal or intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from estrogen, anti-estrogens or selective estrogen receptor modulators, androgens, anti-androgens or progestins.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 pieces/ml, not less than 5 ⁇ 10 4 pieces/ml, not less than 7 ⁇ 10 4 pieces/ml, not less than 1 ⁇ 10 5 pieces/ml, not less than 3 ⁇ 10 5 pieces/ ml, not less than 5 ⁇ 10 5 pcs/ml, not less than 7 ⁇ 10 5 pcs/ml, not less than 1 ⁇ 10 6 pcs/ml, not less than 3 ⁇ 10 6 pcs/ml, not less than 5 ⁇ 10 6 pieces/ml, not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml , Not less than 7 ⁇ 10 7 pieces/ml, not less than 1 ⁇ 10 8 pieces/m
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • Male reproductive system diseases include abnormal urination, pyuria, abnormal urethral discharge, pain, lumps, sexual dysfunction, and male infertility related to urological diseases.
  • Mainly inflammation of the urinary system, such as cystitis, urethritis, urinary incontinence, urinary retention, etc.; inflammation of the reproductive system, such as testicular epididymitis, seminal vesiculitis, prostatitis, etc.; genital tuberculosis, such as testicular epididymal tuberculosis, seminal vesicle tuberculosis, etc.; reproduction Tract injuries, such as testicular contusion, penile fracture, urethral rupture, etc.; male infertility diseases, such as varicocele, asthenospermia, congenital vas deferens obstruction, absent vas deferens, etc.; male sexual dysfunction diseases, such as Male erectile dysfunction, premature ejaculation, loss of
  • male infertility refers to infertility caused by male factors. Generally, cohabiting after marriage for more than 2 years without taking any contraceptive measures and the woman is not pregnant. Male infertility includes testicular atrophy, testicular hypoplasia, and lack of sperm. Syndrome, spermatogenesis disorder, azoospermia, obstructive azoospermia, asthenospermia, Klinefelter syndrome, XYY syndrome, Kallmann's syndrome, selective LH deficiency and FSH deficiency, adrenal hyperplasia, hyperplasia Prolactinemia, varicocele, sperm deformity, etc.
  • oligospermia means that the number of sperm in the semen is lower than that of normal healthy and fertile men, including endocrine dysfunction, reproductive system infection, varicocele, anti-sperm antibodies, cryptorchidism, and anti-sperm antibodies. Oligospermia caused by membrane effusion, malnutrition, chemotherapy, radiotherapy, obesity, etc.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of medicaments for the prevention, treatment, delay and/or alleviation of male reproductive system diseases; or, the present invention provides The method for preventing, treating, delaying and/or alleviating male reproductive system diseases comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the male reproductive system disease is azoospermia or oligospermia.
  • the mesenchymal stem cell population of the present invention can be used in azoospermia to increase sperm concentration, improve sperm motility, restore testes and/or restore seminal vesicle functions.
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the pharmaceutical composition of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain embodiments, the administration is by intratesticular or seminiferous tubule or intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from estrogen, anti-estrogens or selective estrogen receptor modulators, androgens, anti-androgens.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 pieces/ml, not less than 5 ⁇ 10 4 pieces/ml, not less than 7 ⁇ 10 4 pieces/ml, not less than 1 ⁇ 10 5 pieces/ml, not less than 3 ⁇ 10 5 pieces/ ml, not less than 5 ⁇ 10 5 pcs/ml, not less than 7 ⁇ 10 5 pcs/ml, not less than 1 ⁇ 10 6 pcs/ml, not less than 3 ⁇ 10 6 pcs/ml, not less than 5 ⁇ 10 6 pieces/ml, not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml , Not less than 7 ⁇ 10 7 pieces/ml, not less than 1 ⁇ 10 8 pieces/m
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the present invention also provides a product for preventing, treating, delaying and/or reducing male reproductive system diseases, which contains the mesenchymal stem cell population of the present invention.
  • the product further contains an additional active ingredient, and the additional active ingredient is as defined above.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the product is an injection, a microinjection, a mucosal patch, an enema, a suppository, a gel, an oral agent, an aerosol, a drop, an ointment, an embedding agent, or a capsule.
  • the product is an implant.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for the prevention and/or treatment of digestive system diseases; or, the present invention provides prevention and/or treatment
  • the method for a digestive system disease includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or the culture supernatant thereof to a subject in need thereof.
  • the digestive system disease is selected from esophageal disease, stomach disease, intestinal disease, liver disease, gallbladder disease, pancreatic disease, or any combination thereof.
  • Intestinal diseases are selected from duodenal ulcer, functional colon disease, intestinal polyps, colon cancer, rectal cancer, inflammatory bowel disease (IBD), colitis, proctitis, irritable bowel syndrome, dyspepsia, functional constipation , Gastroesophageal reflux disease, esophagitis, peritonitis, autoimmune liver disease, gastritis, tuberculous bowel disease or any combination thereof.
  • IBD inflammatory bowel disease
  • colitis proctitis
  • irritable bowel syndrome dyspepsia
  • functional constipation Gastroesophageal reflux disease
  • esophagitis peritonitis
  • autoimmune liver disease gastritis
  • tuberculous bowel disease or any combination thereof.
  • the intestinal disease is an intestinal inflammatory disease.
  • the intestinal inflammatory disease is selected from inflammatory bowel disease (IBD), colitis, proctitis, or any combination thereof.
  • IBD inflammatory bowel disease
  • the intestinal inflammatory disease is inflammatory bowel disease (IBD).
  • IBD inflammatory bowel disease
  • Gastrointestinal diseases mainly refer to general inflammatory gastrointestinal diseases (acute and chronic gastritis, acute and chronic appendicitis, etc.), peptic ulcer, gastric cancer, esophageal cancer, colorectal cancer and irritable bowel Syndrome etc.
  • Inflammatory bowel disease is a disease of gastrointestinal diseases.
  • Liver disease is the general term for all diseases that occur in the liver. According to the different causes of liver damage, it is divided into viral liver diseases, including hepatitis A, hepatitis B, hepatitis C, hepatitis E, etc., as well as metabolic liver disease, alcoholic liver disease, drug or toxic liver disease, and non-alcoholic fatty liver disease. Autoimmune liver disease, etc. According to the speed of onset, it is divided into chronic liver disease and acute liver disease.
  • Liver disease is selected from liver damage, liver fibrosis, hepatitis (such as viral hepatitis A, hepatitis B, viral hepatitis C), liver cirrhosis, liver failure, liver abscess, liver cyst, intrahepatic hemangioma , Liver cancer, intrahepatic bile duct stones, liver fluke disease, liver hydatid disease, alcoholic liver disease, non-alcoholic fatty liver disease, or any combination thereof.
  • hepatitis such as viral hepatitis A, hepatitis B, viral hepatitis C
  • liver cirrhosis such as viral hepatitis A, hepatitis B, viral hepatitis C
  • liver cirrhosis such as viral hepatitis A, hepatitis B, viral hepatitis C
  • liver cirrhosis such as viral hepatitis A, hepatitis B, viral hepatitis C
  • Liver diseases include fatty liver.
  • fatty liver refers to a pathological change of excessive fat accumulation in liver cells due to various reasons. It is a common liver pathological change, rather than an independent disease.
  • Fatty liver is generally divided into two categories: alcoholic fatty liver and non-alcoholic fatty liver.
  • Liver diseases include steatohepatitis.
  • the term "steatohepatitis” belongs to a type of fatty liver. Mild fatty liver generally has no obvious liver damage and no obvious symptoms. Moderate to severe fatty liver is usually accompanied by liver cell damage, called steatohepatitis, which has corresponding clinical symptoms.
  • Liver diseases include non-alcoholic fatty liver disease.
  • non-alcoholic fatty liver disease refers to a clinicopathological syndrome characterized by excessive deposition of fat in liver cells caused by alcohol and other clear liver damage factors. , Acquired metabolic stress liver injury closely related to insulin resistance and genetic susceptibility. Including simple fatty liver, non-alcoholic steatohepatitis and related cirrhosis.
  • Liver diseases include non-alcoholic steatohepatitis.
  • non-alcoholic steatohepatitis is an inflammatory subtype of non-alcoholic fatty liver disease, accompanied by liver steatosis and evidence of liver cell damage (ballooning) and inflammation , With or without liver fibrosis. Over time, non-alcoholic steatohepatitis may progress to liver fibrosis, cirrhosis, end-stage liver disease, or need liver transplantation.
  • liver diseases include liver steatosis.
  • hepatic steatosis refers to the appearance of fat droplets in the cytoplasm of liver cells.
  • fatty degeneration of the liver occurs, it is mild and there is no obvious visual abnormality.
  • the liver can be seen enlarged, the texture is soft, the color is pale yellow to earthy yellow, the cut surface structure is fuzzy, and there is a greasy feeling. It can be seen under the microscope that vacuoles of different sizes appear in the degenerated liver cytoplasm, which can fuse into a large vacuole in severe cases, resembling fat cells.
  • Liver diseases include liver damage.
  • the liver injury is selected from acute liver injury, chronic liver injury, chemical liver injury, physical liver injury, or any combination thereof.
  • the term "liver injury” is the result of pathological changes caused by various liver diseases.
  • Liver damage caused by various harmful factors mainly includes viral liver damage, alcoholic liver damage and drug-induced liver damage.
  • the liver injury is acute liver injury.
  • the medicament further comprises a carrier or excipient.
  • the carrier is selected from gelatin, chitosan, sodium alginate, collagen, silk protein, cellulose, fibrin, polylactic acid, polyurethane, polyethylene oxide, polyethylene glycol, poly Lactate glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix, decellularized scaffold, or any combination thereof.
  • the carrier is selected from gelatin, collagen, or any combination thereof.
  • the medicament further comprises a second active ingredient.
  • the second active ingredient is selected from the group consisting of vinpromine, choline chloride, inositol, dehydrocholic acid, magnesium sulfate, polyene phosphatidylcholine (Yisanfu), glucuronic acid Ester (Gan Tyler), Glutathione (Guladine, Atomolan), Tiopronin (Kessile), Glycyrrhizin preparations, Adenoglycine (Simetel), Hepatocellular growth factor , Schisandra (bifendate), silymarin (Shuilinjia, Liganlong, Baoganning), oleanolic acid (ganshu tablets), Junzhihuang preparation, Yinchen or any combination thereof.
  • the second active ingredient is selected from aminosalicylic acid drugs, corticosteroid drugs, immunosuppressive agents, biological agents, or any combination thereof.
  • the aminosalicylic acid drug is 5-aminosalicylic acid.
  • the corticosteroid drug is a glucocorticoid.
  • the immunosuppressive agent is selected from azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus, or any combination thereof.
  • the biological agent is a TNF antagonist.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 pieces/ml, not less than 5 ⁇ 10 4 pieces/ml, not less than 7 ⁇ 10 4 pieces/ml, not less than 1 ⁇ 10 5 pieces/ml, not less than 3 ⁇ 10 5 pieces/ml, Not less than 5 ⁇ 10 5 /ml, not less than 7 ⁇ 10 5 /ml, not less than 1 ⁇ 10 6 /ml, not less than 3 ⁇ 10 6 /ml, not less than 5 ⁇ 10 6 pieces/ml, not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml, no Less than 7 ⁇ 10 7 pieces/ml, not less than 1 ⁇ 10 8 pieces/ml, not less than 3 ⁇ 10 8 pieces/ml,
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the route of administration of the mesenchymal stem cells is selected from injection administration, smear administration, paste administration, enema administration, perfusion administration, rectal administration, and oral administration.
  • the method further comprises administering a second active ingredient to a subject in need thereof, the second active ingredient being as described or defined above.
  • the subject is a mammal, such as a human.
  • the present invention provides a product for treating digestive system diseases, which comprises a first active ingredient mesenchymal stem cell population.
  • the mesenchymal stem cell population is as described or defined previously.
  • the digestive system disease is as previously described or defined.
  • the product further comprises a second active ingredient.
  • the second active ingredient is as previously described or defined.
  • the first active ingredient and the second active ingredient are present alone or in combination.
  • the first active ingredient is administered in combination with a second active ingredient selected from the foregoing.
  • the product is an implant.
  • the implant is used to improve the microenvironment and suppress immune rejection.
  • the subject is a mammal, such as a human.
  • acute liver injury refers to acute injury or necrosis of liver cells in a short period of time, abnormal liver function, and liver failure in some patients.
  • the main causes of the acute liver injury include viral infection, improper drug administration, food additives, excessive intake of ethanol, mistaking of toxic food, radiation damage, and the like.
  • Acute liver injury includes viral, chemical, and drug-induced liver injury.
  • chemical acute liver injury refers to liver injury caused by chemical hepatotoxic substances. These chemicals include alcohol, chemical toxic substances in the environment (such as carbon tetrachloride) and certain drugs.
  • liver has strong defense and repair capabilities. When liver damage is caused by various reasons, it can rely on liver cell regeneration to rebuild liver structure and restore liver function.
  • Acute liver injury is a type of disease characterized by liver insufficiency in a short period of time caused by viruses, drugs, alcohol, autoimmune abnormalities and other factors. The main pathological changes are extensive necrosis and apoptosis of liver cells, making the liver unable to perform normal synthesis. And metabolic function. If the disease progresses within a short period of time without intervention, it can quickly deteriorate and develop coagulation dysfunction, jaundice, ascites, and hepatic encephalopathy, which can lead to multiple organ failure.
  • the present invention relates to the use of a mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of acute liver injury in a subject, or in the preparation of Use in a medicine for preventing and/or treating acute liver injury in a subject.
  • the above uses can protect the liver, maintain and/or extend and/or improve liver function.
  • the pharmaceutical composition can inhibit or reduce the rate of weight loss of patients with acute liver injury, and reduce the mortality of patients with acute liver injury.
  • the pharmaceutical composition can reduce the content of transaminase and/or alkaline phosphatase in serum.
  • the pharmaceutical composition can prevent inflammatory cell infiltration.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the culture supernatant of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds, or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, fiber Plain polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Non-alcoholic steatohepatitis also known as metabolic steatohepatitis
  • NASH is a progressive form of non-alcoholic fatty liver disease, defined as the presence of 5% or more of liver steatosis with inflammation and liver cell damage ( For example, ballooning), with or without fibrosis.
  • NASH can easily develop into diseases such as liver cirrhosis and liver cancer.
  • the number of patients with liver cirrhosis in China is approximately 1.09 million, which will increase to 2.32 million in 2030.
  • NASH is closely related to heredity (polymorphism of PNPLA3), living habits (eating habits of the host, the number of meals, sleep-wake cycles, etc.), obesity, and metabolic syndrome.
  • Common symptoms of NASH include lack of appetite, fatigue, abdominal distension, nausea and vomiting, dull pain in the liver area, and hepatomegaly.
  • Environmental, metabolic, and genetic factors cause free fatty acids to accumulate in the liver, which in turn causes a series of damage to cells.
  • the former includes changing lifestyle habits to improve the course of the disease, while the latter includes liver transplantation, surgery, and drugs under research to treat the disease.
  • the treatment strategy of developing a healthy lifestyle is more suitable for adjuvant treatment. Liver transplantation is expensive and donors are scarce; surgical treatment requires patients to meet the enrollment conditions, which has limitations; there are currently no therapeutic drugs approved by the FDA that can be used for NASH. Therefore, the treatment of NASH is still in a state of desperation.
  • the present invention relates to the use of a mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of non-alcoholic steatohepatitis in a subject, or It is prepared for preventing non-alcoholic steatohepatitis in subjects, or delaying or reducing non-alcoholic steatohepatitis, or preventing reduction of non-alcoholic steatohepatitis.
  • the pharmaceutical composition can reduce the weight of the liver, inhibit the accumulation of fat in the liver, and/or reduce the steatosis of the liver.
  • the pharmaceutical composition can reduce the content of transaminase and improve liver function.
  • the pharmaceutical composition can inhibit fibrosis, and/or inhibit inflammation.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In some preferred schemes, it can be administered intravenously.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds, or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin , Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • IBD Inflammatory bowel disease
  • IBD Crohn’s disease
  • UC ulcerative colitis
  • IBD Intestinal complications of IBD include abscess, intestinal obstruction, intestinal perforation, colorectal cancer, anal fissure, fistula, worsening menstrual symptoms, and toxic megacolon. Certain complications of IBD (Crohn's disease and ulcerative colitis) can be life-threatening and require prompt treatment to prevent more serious diseases.
  • Abscesses that are more common in Crohn's disease than in ulcerative colitis are the accumulation of pus at the site of infection. It may occur in the invisible body, such as inside the intestinal wall, outside the intestinal wall, skin, etc. Internal abscesses can be resolved with antibiotic treatment, but if they cannot be resolved, they need to be drained. This can be done by inserting a catheter through the skin into the abscess site. The catheter can be inserted in other ways, such as through the stomach wall. In some cases, surgery is required to drain pus.
  • Intestinal obstruction refers to the partial or complete obstruction of a part of the small or large intestine, preventing the discharge of body waste. Obstruction is usually accompanied by severe pain, vomiting and constipation. In some cases, a nasogastric tube can help relieve symptoms, but surgery may be required to remove the obstruction.
  • Bowel perforation The risk of perforation (hole) in the intestine is rare, but this is a potentially fatal complication of IBD. Perforation is most common during the first episode of ulcerative colitis and in people whose intestinal walls become thin due to severe illness. Perforations are most often treated with surgery to repair the hole or even remove part of the intestine.
  • Colorectal cancer IBD patients have an increased risk of colorectal cancer, especially those who have had total colonic ulcerative colitis for 8 to 10 years. Crohn's disease patients are also at risk, although there is little information about the degree of risk. For anyone with IBD, especially those at the highest risk, colonoscopy must be carefully monitored for colorectal cancer.
  • Anal fissure An anal fissure is a painful tear in the anal canal that can cause bleeding. Most cracks can be healed without surgery. Treatments such as topical creams can be used to ensure smooth bowel movements without tension. Cracks that cannot heal and become chronic may require surgery.
  • Fistula A fistula is an abnormal connection between two body cavities or between a body cavity and the skin. In Crohn’s disease, fistulas are more common than in ulcerative colitis. In fact, about 25% of Crohn’s disease patients may develop a fistula at some point in the course of the disease. Certain fistulas can be treated with medication, but the more severe or extensive they are, the more likely they are to require surgery.
  • Premenstrual syndrome Some women with IBD notice that their symptoms worsen during their menstrual period. Before and during menstrual cramps, diarrhea and pain may increase. The cause of these symptoms may be an increase in hormones during the menstrual cycle.
  • Toxic megacolon is rare, but it is a life-threatening disease. If left untreated, the toxic megacolon may cause shock, perforation, or infection of the abdomen or blood. In some cases, medical treatment is possible, but in severe cases, surgery may be required.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant and/or pharmaceutical composition as described herein for the prevention and/or treatment of inflammatory bowel disease in a subject, or in Preparation of a medicament for preventing and/or treating inflammatory bowel disease in a subject.
  • the above uses can prevent and treat the infiltration of inflammatory cells, protect the colon, reduce inflammatory factors (such as IFN- ⁇ , IL-6, TNF- ⁇ , iNOS, etc.), increase or upregulate anti-inflammatory factors (such as IL10, etc.), and inhibit inflammation.
  • inflammatory factors such as IFN- ⁇ , IL-6, TNF- ⁇ , iNOS, etc.
  • anti-inflammatory factors such as IL10, etc.
  • Produce and secrete nutritional factors such as VEGF, HGF, SDF-1a, etc.
  • promote colon tissue repair and other functions in order to inhibit inflammation and promote tissue repair in the prevention and/or treatment of inflammatory bowel disease, thereby protecting the colon Organize, protect the intestines, and improve tissue repair capabilities.
  • the pharmaceutical composition can be used to treat Crohn's disease (CD) and/or ulcerative colitis (UC).
  • CD Crohn's disease
  • UC ulcerative colitis
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the culture supernatant of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like.
  • the pharmaceutical composition is administered by intravenous injection or intraperitoneal injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose Polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the pharmaceutical composition also includes other drug combinations, including but not limited to 5-aminosalicylic acid, NF- ⁇ B and Activator protein-1 ((Activator protein-1, AP1), immunosuppressive agents).
  • Drugs Azathioprine, 6-mercaptopurine, Methotrexate, Cyclosporin A, Tacrolimus), tumor necrosis Factors (Tumor necrosis factor, TNF), antagonists, etc.
  • the present invention provides the use of the mesenchymal stem cell population or the culture supernatant thereof in the preparation of a medicament for the prevention and/or treatment of neurological diseases; or, the present invention provides prevention and/or treatment
  • the method for neurological diseases includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or the culture supernatant thereof to a subject in need thereof.
  • Nervous system disease is a disease with nervous system dysfunction as the main manifestation.
  • the symptoms mainly include abnormal mental behavior, forgetfulness, insomnia, emotional changes, and intellectual changes.
  • cerebrovascular diseases degenerative diseases of the nervous system, infectious diseases of the central nervous system, demyelinating diseases of the central nervous system, movement disorders, epilepsy, spinal cord diseases, genetic diseases of the nervous system, abnormal development of the nervous system diseases, central nervous system Systemic toxic diseases, central nervous system tumor diseases, central nervous system immune diseases, etc.
  • Examples include cerebrovascular disease, periodic paralysis, progressive muscular dystrophy, myotonic muscular dystrophy, ataxia, insomnia, neurasthenia, epilepsy, trigeminal neuralgia, neurodegenerative diseases, neuropathic headache (e.g., migraine Headache, etc.) and neuropathy, etc.
  • Neuropathy is a disease in which the sensory, motor, consciousness, and plant nerve dysfunctions of the central nervous system, peripheral nervous system, and autonomic nervous system are clinical manifestations.
  • Neurodegenerative diseases refer to the gradual loss of neuron structure or function or even death leading to dysfunction, including amyotrophic lateral sclerosis, Parkinson, Alzheimer's disease, epilepsy, Huntington's disease and spinal muscle Atrophy, brain damage, different types of spinocerebellar ataxia, dentate nucleus red nucleus pallidus subthalamic nucleus atrophy, infectious spongiform encephalopathy, primary lateral sclerosis, multiple sclerosis, cardiovascular and cerebrovascular dementia, Neuropathic pain, glaucoma, traumatic spinal cord injury, multiple system atrophy, etc.
  • ALS Amyotrophic lateral sclerosis
  • Amyotrophic lateral sclerosis (Amyotrophic lateral sclerosis, ALS), commonly known as “gradual freezing", is a spontaneous and fatal neurodegenerative disease that affects the upper motor neurons of the brain's motor cortex, the brain stem, and the spinal cord. Lower motor neuron. The loss of a large number of motor neurons can cause muscle atrophy and spontaneous contraction and spasm. ALS is divided into two categories: familial ALS (Familial ALS, FALS) and sporadic ALS (Sporadic ALS, SALS), the former accounted for 10%, and the latter accounted for 90%.
  • the age of onset of ALS patients is usually after 40 years old, 47-52 years old and 58-63 years old are the high-incidence stages of FALS and SALS respectively. After 80 years of age, the incidence rate decreases, and men are more likely to get the disease than women. Since the onset of the disease, the patients are average. The survival time is 3-5 years. Various factors are closely related to the onset of ALS, such as genetics, occupation, lifestyle, age, etc.
  • the onset of ALS is the failure of astrocytes to recover the glutamate accumulated in the synapses in time, resulting in glutamate excitotoxicity;
  • the mutated genes include SOD1, UBQLN2, OPTN, VCP, TDP43, FUS, C9ORF72 leads to the production of wrong protein conformation polymers, which are toxic and produce toxic RNA species, which aggravate motor nerve damage, causing synapses to retract, unable to bind to postsynaptic membrane receptors, and unable to complete electrical signal transmission, and finally appeared Clinical characterization.
  • the treatment of ALS there are drug treatments.
  • the drug of the present invention can be administered by intravenous injection or brain tissue injection in addition to the aforementioned administration forms.
  • the drug can delay onset.
  • the drug can enhance the coordination ability, movement ability, and reaction ability of the limbs, such as grasping power and the like.
  • the drug can improve muscle strength in amyotrophic lateral sclerosis and reduce motor neuron damage.
  • the drug can reduce motor neurons in amyotrophic lateral sclerosis, reduce microglia and astrocytes, and reduce disease progression.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the culture supernatant of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like.
  • the combination of drugs is by intravenous injection or brain tissue injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid, elastic Protein, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Epilepsy refers to a chronic brain disease that is caused by a variety of causes and is characterized by sudden, repeated and transient central nervous system dysfunctions caused by excessive discharge of brain neurons. Including idiopathic epilepsy syndrome, symptomatic epilepsy syndrome, possible symptomatic epilepsy syndrome or cryptogenic epilepsy, reflex epilepsy syndrome, benign epilepsy syndrome, epileptic encephalopathy.
  • Epilepsy is a chronic brain disease that manifests as recurrent seizures, which can suddenly seize for no reason. It is the second most common neurological disease after stroke.
  • the "abnormal discharge" of brain neurons causes epileptic seizures, which are repetitive and transient.
  • Epilepsy affects more than 70 million people worldwide. The incidence in the Chinese population is between 5-7 ⁇ , and there are 6.5-9.1 million patients nationwide. Some cerebrovascular complications, head trauma, central nervous system infection, etc. can cause secondary epilepsy; sleep, age, genetics and idiopathic seizures are closely related.
  • antiepileptic drugs are the most widely used.
  • the present invention relates to mesenchymal stem cell populations, cultures, culture supernatants or pharmaceutical compositions as described herein in preparation for preventing and/or treating epilepsy, delaying or reducing epileptic seizures, or preventing epileptic seizures Use in medicine; or, the present invention relates to a method for preventing and/or treating epilepsy, delaying or reducing epileptic seizures, or preventing epileptic seizures, which comprises administering to a subject in need thereof an effective amount of the time as described herein Mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition.
  • the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition of the present invention can prevent epilepsy, or delay or reduce epileptic seizures or prevent epileptic seizures.
  • the administration is via cerebral or intravenous injection.
  • the drug combination can increase the number of GABAergic neurons in the brain or activate GABAergic neurons or reduce the number of microglia or remodel and repair the neural circuits of GABAergic neurons in the model or promote The ability of endogenous stem cells to differentiate into GABAergic lineage or inhibit inflammation.
  • the drug combination can improve the memory and learning ability of model animals.
  • the drug combination can provide the secretion level of nutrient molecules (such as GDNF) in the brain and protect nerve function.
  • nutrient molecules such as GDNF
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the culture supernatant of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like. In certain preferred schemes, the administration can be via brain or intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug may be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • AD Alzheimer's disease
  • AD Alzheimer's disease
  • a ⁇ extracellular amyloid
  • NTFs neurofibrillary tangles
  • the present invention relates to the preparation of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for preventing and/or treating Alzheimer’s disease or cerebrovascular disease, delaying or reducing Alzheimer’s disease.
  • Alzheimer’s disease or cerebrovascular disease or prevent the use of drugs for reducing Alzheimer’s disease or cerebrovascular disease; or, involving the prevention and/or treatment of Alzheimer’s disease or cerebrovascular disease, delaying or alleviating Alzheimer’s disease Murder disease or cerebrovascular disease, or a method for preventing the alleviation of Alzheimer’s disease or cerebrovascular disease, which comprises administering to a subject in need thereof an effective amount of the mesenchymal stem cell population, culture, Culture supernatant or pharmaceutical composition.
  • the drug can improve learning and memory abilities, and improve memory and cognitive deficits.
  • the drug can reduce the accumulation of starch deposits in the brain and reduce the adverse effects of starch deposits on nerves.
  • the drug can inhibit the conversion of microglia to a pro-inflammatory form, and prevent the excessive activation and dysfunction of microglia.
  • the drug can improve the phagocytic ability of microglia, remove amyloid deposits and apoptotic cell debris, inhibit the production of A1 astrocytes in the inflammatory environment of the AD brain, and inhibit over-activated immunity .
  • the drug can increase nerve survival and improve cognition and memory.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • the drug is in a unit dosage form, and the unit dose of the drug contains 1 ⁇ 10 4 pieces/ml (for example, not less than 1 ⁇ 10 4 pieces/ml, not less than 3 ⁇ 10 4 Pcs/ml, not less than 5 ⁇ 10 4 pcs/ml, not less than 7 ⁇ 10 4 pcs/ml, not less than 1 ⁇ 10 5 pcs/ml, not less than 3 ⁇ 10 5 pcs/ml, no less Less than 5 ⁇ 10 5 /ml, not less than 7 ⁇ 10 5 /ml, not less than 1 ⁇ 10 6 /ml, not less than 3 ⁇ 10 6 /ml, not less than 5 ⁇ 10 6 /ml, not less than 7 ⁇ 10 6 pieces/ml, not less than 1 ⁇ 10 7 pieces/ml, not less than 3 ⁇ 10 7 pieces/ml, not less than 5 ⁇ 10 7 pieces/ml, not less than 7 ⁇ 10 7 pieces/ml, not less than 7 ⁇ 10 7 pieces/ml, not less than 1
  • the medicine also contains a pharmaceutically acceptable carrier or excipient; preferably, the carrier is selected from gelatin, chitosan, sodium alginate, collagen, silk protein, cellulose, fiber Protein, polylactic acid, polyurethane, polyethylene oxide, polyethylene glycol, polylactic acid glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix, decellularized scaffold and any combination thereof; preferably Preferably, the carrier is selected from gelatin, collagen, and any combination thereof; preferably, the drug is injection, microinjection, mucosal patch, enema, suppository, gel, oral agent, aerosol, drops,
  • the ointment, embedding agent or capsule is preferably an injection; preferably, the medicament further contains a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution, dispersion, suspension or emulsion.
  • the drug also contains other active ingredients, for example, the other active ingredients are selected from ⁇ -secretase inhibitors (such as OM99-2), ⁇ -secretase inhibitors (such as R-flurbiprofen) , Cholinesterase inhibitors (such as donepezil, donepezil hydrochloride, rivastigmine, huperzine A, tacrine, galantamine or galantamine hydrobromide), M choline receptor agonists Or antagonists (for example, M1 cholinergic receptor agonists include Xianomeline, Salcomeline, Nabiracetam, AF-102B and SR-46559A; M2 cholinergic receptor antagonists include BIBN-99 and AF- DX 11; or N-choline receptor agonists include nicotine and ABT-418), glutamate receptor antagonists (such as memantine, memantine hydrochloride or riluzole), calcium antagonists (such as nimodipine) Or
  • vitamin E propargyl, melatonin, melatonin, desferrioxamine, idebenone, or tirapazate mesylate
  • drugs that inhibit A ⁇ production e.g., estrogen Hormones, chloroquine, Congo red or phenylacetate
  • dopamine substitutes e.g. levodopa
  • peripheral decarboxylase inhibitors e.g. carbidopa or benserazide
  • dopamine D receptor agonists e.g. bromocriptine
  • Patina pergolide, apomorphine, pramipexole, or ropinirole
  • neurotrophic agents e.g.
  • Anticholinergic drugs such as diphenhydrazine, procyclidine, biperiden, or benzatropine
  • antidepressants such as amitriptyline, phenelzine, tranylcypromine, isocarboxazid, or ittrex
  • Theophylline serotonin and winter (e.g. sarizotan or budibine), MAO-B inhibitors (e.g. selekline or rasacline), dopamine ⁇ -hydroxylase inhibitors (e.g. Fusarium Bacteric acid), COMT inhibitors (e.g.
  • immunosuppressive agents e.g. azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A or tacrolimus
  • Any combination preferably, the mesenchymal stem cell population and the other active ingredients exist alone or in combination.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration is via cerebral or intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the dose administered is not less than 1 ⁇ 10 4 /time (for example, not less than 1 ⁇ 10 4 /time, not less than 3 ⁇ 10 4 /time, not less than 5 ⁇ 10 4 /time, not less than 7 ⁇ 10 4 /time, not less than 1*10 5 /time, not less than 3*10 5 /time, not less than 5*10 5 /time, Not less than 7*10 5 /time, not less than 1 ⁇ 10 6 /time, not less than 3 ⁇ 10 6 /time, not less than 5 ⁇ 10 6 /time, not less than 7 ⁇ 10 6 /time, not less than 1 ⁇ 10 7 /time, not less than 3 ⁇ 10 7 /time, not less than 5 ⁇ 10 7 /time, not less than 7 ⁇ 10 7 /time, no Less than 1 ⁇ 10 8 /time, not less than 3 ⁇ 10 8 /time, not less than 5 ⁇ 10 8 /time, not less than 7 ⁇ 10 8 /time, not less than 1 ⁇ 10 9 Number/time,
  • a prophylactic and/or therapeutically effective amount of mesenchymal stem cell population is administered to a subject through the following routes: injection administration, mucosal administration, cavity administration, oral administration, respiratory administration Or skin administration.
  • the method further comprises simultaneously, sequentially or alternately administering to the subject a prophylactic and/or therapeutically effective amount of other active ingredients, such as selected from ⁇ -secretase inhibitors (such as OM99 -2), gamma secretase inhibitors (e.g. R-flurbiprofen), cholinesterase inhibitors (e.g. donepezil, donepezil hydrochloride, rivastigmine, huperzine A, tacrine, galanta Or Galantamine hydrobromide), M choline receptor agonists or antagonists (e.g.
  • ⁇ -secretase inhibitors such as OM99 -2
  • gamma secretase inhibitors e.g. R-flurbiprofen
  • cholinesterase inhibitors e.g. donepezil, donepezil hydrochloride, rivastigmine, huperzine A, tacrine, galanta Or Galantamine hydrobromide
  • M1 choline receptor agonists include Xianomeline, Sacomeline, Nabiracetam, AF-102B and SR-46559A; M2 cholinergic receptor antagonists include BIBN-99 and AF-DX 11; or N cholinergic receptor agonists include nicotine and ABT-418), glutamate receptor antagonists (such as memantine, Memantine hydrochloride or riluzole), calcium antagonists (e.g. nimodipine or flunarizine), antioxidants (e.g.
  • vitamin E propargyl, melatonin, melatonin, desferrioxamine, ideben) Quinone or Tirazat mesylate
  • drugs that inhibit A ⁇ production e.g., estrogen, chloroquine, Congo red, or fenprofen
  • dopamine substitutes e.g., levodopa
  • peripheral decarboxylase inhibitors e.g., Kabi Dopa or benserazide
  • dopamine D receptor agonists e.g. bromocriptine, pergolide, apomorphine, pramipexole, or ropinirole
  • neurotrophic agents e.g.
  • piperacetam anil Racetam, Oxiracetam, Pramiracetam, or Nefiracetam
  • anticholinergics e.g. diphenhexol, procyclidine, biperiden, or benztropine
  • antidepressants e.g. amitripty Lin, phenelzine, tranylcypromine, isocarboxazid or ittrafylline
  • serotonin and winter e.g. sarizotan or buddypine
  • MAO-B inhibitors e.g. selekline or Rasaclan
  • dopamine ⁇ -hydroxylase inhibitors e.g. fusaric acid
  • COMT inhibitors e.g. encatapone or tolcapone
  • immunosuppressive agents e.g. azathioprine, 6-mercaptopurine
  • Methotrexate cyclosporine A or tacrolimus
  • Extrapyramidal tract and movement disorders including Parkinson’s disease, secondary Parkinson’s syndrome, Parkinson’s syndrome caused by diseases classified elsewhere, other degenerative diseases of the basal ganglia, dystonia, other extrapyramidal tracts and Movement disorders, extrapyramidal tracts and movement disorders caused by diseases classified elsewhere.
  • Movement disorders also known as extrapyramidal diseases, mainly manifest the dysfunction of voluntary movement regulation, and muscle strength, sensation and cerebellar function are not affected.
  • This group of diseases originates from basal nucleus dysfunction, and is usually divided into two categories: increased muscle tone-reduced exercise and decreased muscle tone-excessive exercise. The former is characterized by lack of exercise, and the latter mainly manifests abnormal involuntary movements.
  • Parkinson's Disease is a movement disorder disease, a chronic neurodegenerative disease that affects the central nervous system, and mainly affects the motor nervous system. Its symptoms usually appear slowly over time. The most obvious early symptoms are tremor, limb stiffness, hypokinesia and abnormal gait. There may also be cognitive and behavioral problems; dementia is quite common in patients with severe illness, more than three Major depressive disorder and anxiety will also occur in one in every case. Other possible symptoms include sensory, sleep, and emotional problems. The main motor symptoms caused by Parkinson's disease are collectively called Parkinson's syndrome.
  • the present invention relates to the preparation of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for preventing and/or treating Parkinson’s disease, delaying or reducing Parkinson’s disease, or preventing the reduction of Parkinson’s disease.
  • the drug can reduce dopaminergic denervation, or/and improve the progression of Parkinson's disease.
  • the drug can improve the stiffness of the limbs, or/and enhance athletic ability.
  • the drug can protect neurons, reduce neuronal damage and death, have nourishment and promote synaptic regeneration effects on neurons, reduce inflammation in the brain, or/and improve the microenvironment in the brain.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration is by intravenous or cerebral injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Spine cord injury refers to the transverse injury of the structure and function of the spinal cord caused by various pathogenic factors (trauma, inflammation, tumor, etc.), resulting in spinal cord nerve function below the level of the injured segment (motor, sensory, sphincter and autonomic nerve function) )
  • Disorders divided into primary spinal cord injury and secondary spinal cord injury, the former includes traumatic spinal cord injury, the latter includes spinal tuberculosis, spinal purulent infection, transverse myelitis, spinal degenerative disease, congenital scoliosis , Tethered cord syndrome.
  • SCI Spinal cord injury
  • Secondary injury refers to the secondary damage to the spinal cord caused by spinal cord compression caused by external force, such as spinal cord edema, hematoma formed by small blood vessel hemorrhage in the spinal canal, compression fracture, and broken intervertebral disc tissue.
  • the present invention relates to the mesenchymal stem cell population or its culture supernatant or pharmaceutical composition as described herein for preparing a medicament for preventing and/or treating spinal cord injury, delaying or reducing spinal cord injury, or preventing alleviating spinal cord injury
  • the present invention relates to a method for preventing and/or treating spinal cord injury, delaying or reducing spinal cord injury, or preventing alleviating spinal cord injury, which comprises administering to a subject in need thereof an effective amount of as described herein Mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition.
  • the medicament can improve athletic performance.
  • the drug can reduce bladder outlet resistance and detrusor overactivity, and improve urination function.
  • the drug can promote cell survival and enhance axon regeneration, inhibit glial cell activation, resist fibrosis, and reduce inflammatory responses at the injured site.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry or mixture
  • the drug includes the above-mentioned drugs as well as drugs such as prostacyclin, endothelin-1 receptor antagonist or/and type 5 phosphodiesterase inhibitor.
  • Cerebrovascular disease refers to a group of diseases that occur in the blood vessels of the brain, brain tissue damage and brain dysfunction caused by blood circulation disorders in the brain, including stroke, cerebral palsy, cerebral atherosclerosis, cerebral arteritis, Cerebral artery injury, cerebral aneurysm, intracranial vascular malformation, cerebral arteriovenous fistula, cerebrovascular accident, cerebral vasospasm, etc.
  • Stroke refers to a group of diseases that cause brain tissue damage due to the sudden rupture of blood vessels in the brain or the inability of blood to flow into the brain due to blood vessel obstruction. It includes two types of ischemic and hemorrhagic. Ischemic stroke includes cerebral thrombosis, cerebral embolism, and cerebral infarction; hemorrhagic stroke includes subarachnoid hemorrhage and hypertensive cerebral hemorrhage.
  • Stroke is a type of cerebrovascular disease in which cerebral vascular stenosis, blockage or rupture causes cerebral tissue ischemia or hemorrhage, which leads to the necrosis of brain cells and tissues.
  • ischemic stroke also known as cerebral infarction
  • hemorrhagic stroke including parenchymal hemorrhage, intraventricular hemorrhage and subarachnoid hemorrhage.
  • the incidence of ischemic stroke in men and women is 212/100,000 and 170/100,000; hemorrhagic stroke: 12-15/100,000.
  • people with lifestyles such as smoking, poor diet, inactivity, etc. and those with complications including high blood pressure, diabetes, hyperlipidemia, obesity, etc. are often prone to stroke.
  • t-PA thrombolytic drug tissue plasminogen activator
  • mesenchymal stem cells are basically in phase I and phase II.
  • the present invention relates to mesenchymal stem cell populations, cultures, culture supernatants or pharmaceutical compositions as described herein in preparation for preventing and/or treating stroke, delaying or reducing stroke, or preventing stroke
  • the present invention relates to a method for preventing and/or treating stroke, delaying or reducing stroke, or preventing stroke, which comprises administering an effective amount of as described herein to a subject in need
  • the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition is administered to a subject in need.
  • the drug can reduce the degree of cerebral tissue infarction, reduce the area of cerebral tissue infarction, reduce the water content of brain tissue, increase the use rate of lateral forelimbs, increase exercise time, and reduce the degree of nerve cell damage caused by stroke.
  • the drug can promote neuronal regeneration, reduce neuronal damage and death, provide nutrition to neurons and promote synaptic regeneration.
  • the drug can attenuate the inflammatory response in the brain and improve the microenvironment in the brain.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration is by intravenous injection or brain tissue injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Neuropathic pain refers to pain caused or caused by diseases such as primary disease or dysfunction that affect peripheral nerves, nervous system, sensory nerves, etc., and is characterized by spontaneous pain, allodynia, and hyperalgesia.
  • the disease can be caused by injury to peripheral nerves, posterior root of spinal cord, spinal cord and some parts of the central nerve above it caused by trauma and/or disease.
  • ischemia Pain such as peripheral vascular disease and angina
  • Parkinson’s syndrome-related movement disorders such as tremor, paralysis, rigidity, and movement disorders
  • spinal cord injury-related neuropathic pain discogenic pain
  • occipital Neuropathic pain such as neuropathic pain, sciatica, intercostal neuralgia, cerebrovascular disease, epilepsy, cerebral edema, hydrocephalus, cancerous neuralgia, encephalitis, meningitis, neurodermatitis, neuropathic headache, etc.
  • Neuropathic pain is a difficult-to-treat pain state caused by damage or abnormality of the nervous system. It is pain that occurs in nerve tissue, such as neuritis. This kind of pain is mainly caused by neuropathy, which is characterized by paroxysmal. Sometimes I feel local pain, but there is no pain when I press it. This is the characteristic of neuropathic pain.
  • the general treatment of nerve pain is mainly to use drugs that nourish the nerves and drugs that cooperate with pain relief, and it is best to use it under the guidance of a doctor.
  • the present invention relates to the preparation of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of neuropathic pain or related neuropathic pain, Or it can be used to prevent neuropathic pain, or delay or reduce neuropathic pain, or prevent its use in drugs that relieve neuropathic pain; or, the present invention relates to a prevention and/or treatment of neuropathic pain-related damage or related Neuropathic pain, or preventing neuropathic pain, or delaying, or reducing neuropathic pain, or preventing the method of reducing neuropathic pain, which comprises administering an effective amount of the mesenchymal stem cells described herein to a subject in need thereof Population, culture, culture supernatant or pharmaceutical composition.
  • the pharmaceutical composition can improve the subject's tolerance to pain, tolerance to abnormal cold pain, and promote movement coordination.
  • the pharmaceutical composition can reduce pro-inflammatory factors (IL-1 ⁇ , IL-6, and IL-17) and inhibit inflammatory response.
  • pro-inflammatory factors IL-1 ⁇ , IL-6, and IL-17
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the drug of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Demyelinating diseases are acquired diseases with different etiologies and clinical manifestations, but with similar characteristics.
  • the characteristic pathological changes are the demyelination of nerve fibers and the relatively intact nerve cells.
  • the role of myelin sheath is to protect neurons and enable nerve impulses to be transmitted quickly on neurons. Therefore, the loss of myelin sheath will affect the transmission of nerve impulses.
  • Demyelinating diseases of the central nervous system including multiple sclerosis, other acute disseminated demyelination, and other demyelinating diseases of the central nervous system.
  • Multiple sclerosis is a kind of demyelinating neuropathy in which the insulating material (ie, myelin) on the surface of nerve cells in the brain or spinal cord of the patient is damaged, and the signal transmission of the nervous system is impaired, resulting in A series of possible symptoms affect the patient's activity, mind, and even mental state. These symptoms may include diplopia, impaired vision on one side, muscle weakness, hypoesthesia, or coordination problems.
  • the condition of multiple sclerosis is changeable, and the patient's symptoms may recur or continue to worsen. Between each episode, the symptoms may disappear completely, but permanent nerve damage still exists, which is especially obvious in patients with severe illness.
  • the present invention relates to a mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein in preparation for the prevention and/or treatment of multiple sclerosis, or for the prevention of multiple sclerosis , Or delay or reduce multiple sclerosis, or prevent the use of multiple sclerosis drugs; or, the present invention relates to a prevention and/or treatment of multiple sclerosis, or prevention of multiple sclerosis, or delay , Or reduce multiple sclerosis, or prevent the method of reducing multiple sclerosis, which comprises administering to a subject in need thereof an effective amount of the mesenchymal stem cell population, culture, culture supernatant or Pharmaceutical composition.
  • the drug can reduce spinal cord demyelination.
  • the drug can inhibit inflammation in the spinal cord, reduce the number of astrocytes, protect oligodendrocytes, or/such as alleviate inflammation in spinal cord segments.
  • the drug can reduce the content of pro-inflammatory factors (such as IFN- ⁇ , IL-17, TNF- ⁇ , IL-2), increase anti-inflammatory factors (such as IL-10), and inhibit inflammation.
  • pro-inflammatory factors such as IFN- ⁇ , IL-17, TNF- ⁇ , IL-2
  • anti-inflammatory factors such as IL-10
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the drug of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Neuroinflammation is a peripheral neuroinflammatory and degenerative disease caused by traumatic brain injury, stroke, cerebral hemorrhage and various neurodegenerative diseases. Under normal circumstances, neuroinflammation maintains homeostasis and promotes tissue repair. However, uncontrolled neuroinflammation can be harmful to the brain. Therefore, controlling the harmful inflammatory response is a promising treatment for neurological diseases.
  • Neuroinflammation refers to inflammation caused by the deterioration or deterioration of nerves or nerve groups due to various reasons, including central nerve inflammation and peripheral nerve inflammation caused by poisoning, infection, nutritional and metabolic disorders, immune abnormalities, aging, genetic mutations, etc.
  • Central nervous system infection refers to acute or chronic inflammation caused by various biological pathogens (including viruses, bacteria, rickettsia, spirochetes, parasites, prions, etc.) invading the central nervous system parenchyma, capsule, and blood vessels.
  • pathogens including viruses, bacteria, rickettsia, spirochetes, parasites, prions, etc.
  • Or non-inflammatory diseases including encephalitis, cerebellitis, diencephalitis, brainstemitis, encephalomyelitis, meningoencephalitis, etc. caused by viral, bacterial, fungal, and parasitic infections.
  • bacterial meningoencephalitis refers to inflammation of the pia mater and brain parenchyma caused by bacterial infection, including streptococcus, staphylococcus, pneumococcus, diplococcus, Pasteurella multocida, and pyogenes Meningitis, encephalitis or meningoencephalitis caused by, necrobacterium, proteus, corynebacterium pyogenes, Listeria monocytogenes, etc., as well as craniocerebral trauma caused by the opening of the subdural space, middle ear inflammation, nose-throat Bacterial meningitis, encephalitis, or meningoencephalitis can be caused by inflammation of the head, other local inflammations of the head, and metastasis of the emboli through the lymph or blood after the rupture of the infected foci.
  • the present invention relates to mesenchymal stem cell populations, cultures, culture supernatants or pharmaceutical compositions as described herein in preparation for preventing and/or treating neuroinflammation, delaying or reducing neuroinflammation, or preventing Use in drugs for reducing neuroinflammation; or, involving the prevention and/or treatment of neuroinflammation, delaying or reducing neuroinflammation, or preventing the method of reducing neuroinflammation, which includes administering effective An amount of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein.
  • the drug can reduce pro-inflammatory factors (such as IL-1 ⁇ , IL-6), increase anti-inflammatory factors (such as IL-10), and reduce inflammation.
  • pro-inflammatory factors such as IL-1 ⁇ , IL-6
  • anti-inflammatory factors such as IL-10
  • the drug can promote neuronal regeneration, reduce neuronal damage and death, reduce neuroinflammatory response, and provide nutrients to neurons and promote synaptic regeneration.
  • the drug can attenuate the inflammatory response and improve the nervous system microenvironment.
  • the drug can improve scene memory ability.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In some preferred schemes, it can be administered intravenously.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection, lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Mental disorder refers to the general term for the disorder of brain function, which leads to different degrees of mental activity such as cognition, emotion, behavior, and will. Common are affective mental disorders, brain organic mental disorders and so on. There are many pathogenic factors: congenital heredity, personality characteristics and physical factors, organic factors, social environmental factors and so on.
  • Mental disorders include schizophrenia, manic-depressive mental disorders, manic disorder (delusions, hallucinations), phobias (phobias, anxiety disorders), behavioral volition disorder (obsessive-compulsive disorder), postpartum mental disorders (postpartum psychosis, Postpartum depression, maternal depression), menopausal mental disorders, paranoid mental disorders and mental disorders associated with various organic diseases (delirium, amnestic syndrome, dementia, bulimia nervosa/anorexia, post-traumatic stress) disease).
  • Mood disorder also known as affective mental disorder, refers to a group of diseases characterized by significant and lasting changes in emotion or mood caused by various reasons. Clinically, it is mainly manifested as emotional ups or downs, accompanied by corresponding cognitive and behavioral changes, and psychiatric symptoms such as hallucinations and delusions. Mood disorders include depression, mania, bipolar disorder, persistent mood disorder and dysthymia.
  • Depression also known as depressive disorder, is characterized by significant and lasting depression as the main clinical feature, and is the main type of mood disorder.
  • the main clinical manifestations are physical symptoms such as low mood, slow thinking, decreased volition, cognitive impairment, and sleep disturbance.
  • the present invention relates to mesenchymal stem cell populations, cultures, culture supernatants or pharmaceutical compositions as described herein in preparation for preventing and/or treating depression, or delaying, or reducing depression or preventing alleviation Use in drugs for depression; or, the present invention relates to a method for preventing and/or treating depression, or delaying, or reducing depression, or preventing depression, which comprises administering an effective amount of The mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein.
  • the drug can promote nerve growth and development.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred schemes, the administration is intravenous or cerebral injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the present invention also provides a product for preventing, treating, delaying and/or alleviating neurological diseases, which contains the mesenchymal stem cell population of the present invention.
  • the product further contains an additional active ingredient, and the additional active ingredient is as defined above.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the product is an injection, a microinjection, a mucosal patch, an enema, a suppository, a gel, an oral agent, an aerosol, a drop, an ointment, an embedding agent, or a capsule.
  • the product is an implant.
  • the present invention provides the use of the mesenchymal stem cell population or the culture supernatant thereof in the preparation of a medicament for the prevention and/or treatment of skin diseases; or, the present invention provides the prevention and/or treatment of skin diseases.
  • the method for disease includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant to a subject in need thereof.
  • the skin is the organ with the largest surface area of the human body. It is a key structure that protects internal tissues from mechanical damage, microbial infection, ultraviolet radiation and extreme temperature effects.
  • Skin system diseases include viral skin diseases, bacterial skin diseases, fungal skin diseases, animal skin diseases, physical skin diseases, dermatitis, eczema, drug eruptions, urticaria skin diseases, itchy skin diseases, erythema and scaly skin Disease, connective tissue disease, bullous skin disease, vasculitis skin disease, skin accessory organ disease, pigmented skin disease, hereditary skin disease, skin tumor, sexually transmitted disease.
  • Scaly skin diseases are selected from the group consisting of psoriasis, parapsoriasis, erythema multiforme, erythema ring, pityriasis simplex, pityriasis rosea, pityriasis contiguous, pityriasis asbestos, lichen planus, lichen lustre, rosary Red lichen, sclerosing atrophic lichen, linear lichen, exfoliative dermatitis, or any combination thereof.
  • Psoriasis is a type of erythematous scaly skin disease.
  • Dermatitis is an inflammatory disease of the skin.
  • Dermatitis has obvious skin damage, which usually occurs on the back of the neck or on both sides, elbow fossa, popliteal fossa, forearm, thigh, calf and lumbosacral area, etc. It often appears in slices, which are triangular or polygonal flat-topped papules. The skin is thickened, the skin ridges are raised, and the skin grooves are deepened, resembling lichens, often reddish or light brown. It is manifested as peeling, peeling, thickening, discoloration, and itching when touched. include:
  • Neurodermatitis It is more common in middle-aged and young people, first with severe itching, then skin lesions; the rash is flat papules, lichenoid changes, no exudation; the rashes mostly occur on the neck, extensible limbs, lumbar area, popliteal fossa, vulva ; The course of the disease is chronic, often recurrent.
  • Atopic dermatitis The initial lesions are mostly on the cheeks. At the beginning, they are scattered or clustered small red papules or erythema, gradually increasing, and small blisters, yellow and white scaly crusts can be seen, and there may be exudation, erosion and secondary infection. Severe itching. Chronic manifestations are dry, larger, more raised brown-red papules and rough and scaly brown lichen-like changes, which can be fused into pieces. After scratching, there is often a little exudation, exfoliation and scratches.
  • Summer dermatitis At first, the skin lesions are pinpoint-sized erythema and papules. After scratching due to itching, there may be scratches, blood scabs, skin hypertrophy and hyperpigmentation. There is no erosion and exudation. It is more likely to occur on the extended sides of the limbs of adults. When the temperature drops, the condition improves significantly and can heal on its own. The condition is obviously related to the climate.
  • Seborrheic dermatitis The rash begins as a red small papule around the hair follicle, and gradually develops and merges into yellow-red patches, covered with greasy scales or crusts. Due to the different parts of the lesion, the clinical manifestations are slightly different.
  • Infant seborrheic dermatitis usually starts 1 to 3 months after birth.
  • the top of the head or the entire scalp can be covered with greasy gray-yellow or yellow-brown scabs of varying thickness, which can affect the eyebrow area, nasolabial fold, behind the ears, etc. , Slightly itchy. It usually heals within 3 to 4 weeks. If it does not heal continuously, infection or atopic dermatitis is often complicated.
  • Solar dermatitis is a delayed photoallergic skin disease induced by sunlight.
  • the clinical manifestations of pleomorphic rash may have erythema, papules, blisters, erosions, scaly, and lichenoid changes, usually some kind of rash.
  • Candida dermatitis occurs mostly in skin folds such as the groin, perianal buttock cleft, armpits, and under the breasts of women. It can also occur in the foreskin of the glans and the labia, nail grooves and corners of the mouth. The rash is mostly local skin flushing, mild swelling, surface erosion, and secretions have a peculiar smell. Sometimes it can be dry and desquamated. Pediatric candidal dermatitis also often affects the trunk and neck skin, showing extensive and dense red macules, which look like hot rash. It can invade the mucosa of the oral cavity or vulva at the same time, and there are often cheese-like secretions that are pseudomembranous.
  • Mosquito bite dermatitis It is a dermatitis caused by being bitten by an insect, contacting its venom or the powdered hair of the insect.
  • the more common pests are fleas, lice, midges, spiny caterpillars, moths, mosquitoes, bed bugs, and bees. Symptoms such as erythema, papules, and wind lumps may appear. In severe cases, blisters or bullae may appear, and petechiae or blisters may be seen at the sting site.
  • Hormone-dependent dermatitis is dermatitis caused by long-term and repeated improper external use of hormones. External use of high-efficiency corticosteroids on the same site for more than 3 weeks, skin erythema, papules, dry desquamation, atrophy, atrophic lines, telangiectasia, purpura, acne, abnormal pigmentation, rosacea-like dermatitis, perioral dermatitis, photosensitivity , Hairy, difficult to identify ringworm, secondary symptoms such as ichthyosis-like changes, etc., there is obvious local itching or burning sensation.
  • the medicament further comprises a carrier or excipient.
  • the carrier is selected from gelatin, chitosan, sodium alginate, collagen, silk protein, cellulose, fibrin, polylactic acid, polyurethane, polyethylene oxide, polyethylene glycol, poly Lactate glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix, decellularized scaffold, or any combination thereof.
  • the carrier is selected from gelatin, collagen, or any combination thereof.
  • the medicament further comprises a second active ingredient.
  • the second active ingredient is selected from the group consisting of ebastine tablets, loratadine tablets, cetirizine tablets, mometasone furoate ointment, halometasone ointment, mupirocin ointment, fu Cedic acid ointment, cefixime tablets, roxithromycin tablets, netifene ketoconazole ointment, sertaconazole ointment, itraconazole tablets, terbinafine tablets, acyclovir tablets, valaximate Clovir tablets, penciclovir ointment, interferon gel, or any combination thereof.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 , Not less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 pieces, not less than 3 ⁇ 10 6 pieces, not less than 5 ⁇ 10 6 pieces, not less than 7 ⁇ 10 6 pieces, not less than 1 ⁇ 10 7 pieces, no Less than 3 ⁇ 10 7 pieces, not less than 5 ⁇ 10 7 pieces, not less than 7 ⁇ 10 7 pieces, not less than 1 ⁇ 10 8 pieces, not less than 3 ⁇ 10 8 pieces, not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 109 , not less than 3 ⁇ 109 , not less than 5 ⁇ 109 , not less than 7 ⁇ 109, not less Less than
  • the dose of mesenchymal stem cells is not less than 1 * 10 4 cells / mL ((e.g. not less than 1 ⁇ 10 4, less than 3 ⁇ 10 4, less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 10 7 , not less than 3 ⁇ 10 7 , not less than 5 ⁇ 10 7 , Not less than 7 ⁇ 10 7 , not less than 1 ⁇ 10 8 , not less than 3 ⁇ 10 8 , not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 10 9 , not less Less than 3 ⁇ 10 9 , not less than 5 ⁇ 10 9 , not less than 7 ⁇ 10 9 , not less than 1 ⁇ 10 9 ,
  • the route of administration of the mesenchymal stem cells is selected from injection administration, smear administration, paste administration, enema administration, perfusion administration, rectal administration, and oral administration.
  • the method further comprises administering a second active ingredient to a subject in need thereof, the second active ingredient being as described or defined above.
  • the subject is a mammal, such as a human.
  • the present invention provides a product for treating skin diseases, which comprises a first active ingredient mesenchymal stem cell population.
  • the mesenchymal stem cell population is as described or defined previously.
  • the skin disease is as previously described or defined.
  • the product further comprises a second active ingredient.
  • the second active ingredient is as previously described or defined.
  • the first active ingredient and the second active ingredient are present alone or in combination.
  • the first active ingredient is administered in combination with a second active ingredient selected from the foregoing.
  • the product is an implant.
  • the implant is used to improve the microenvironment and suppress immune rejection.
  • the subject is a mammal, such as a human.
  • AD Atopic dermatitis
  • AD Atopic dermatitis
  • AD is a chronic, recurrent, itchy and inflammatory skin disease.
  • AD has become an important public health problem, with a prevalence rate of up to 20% in children and 3-10% in adults.
  • the pathogenesis of AD is complex and involves many factors such as heredity, immunity and environment. Among them, the abnormal immune function, especially the immune response effect of immune cells, plays an important role in the pathogenesis of AD.
  • the treatment of AD usually involves the local and/or systemic use of glucocorticoids and immunosuppressive agents, but local use of glucocorticoids has limited effect in patients with moderate to severe AD, and systemic use of immune agents has bone marrow suppression and increased infection Opportunity and other risks; research results of new biological agents such as anti-interleukin (IL)-4R monoclonal antibody dupilum-ab and anti-immunoglobulin IgE monoclonal antibody omalizumab (Omalizumab) It is limited and there are differences. Therefore, it is necessary to develop new and safe and effective methods for the treatment of AD.
  • IL-4R monoclonal antibody dupilum-ab
  • IgE anti-immunoglobulin IgE monoclonal antibody omalizumab
  • the present invention relates to the use of a mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of atopic dermatitis in a subject, or in the preparation of It is used to prevent atopic dermatitis in subjects, or delay or reduce atopic dermatitis or prevent atopic dermatitis from alleviating.
  • the present invention provides the treatment of atopic dermatitis by M cells.
  • M cell therapy can improve the microenvironment of mouse skin and inhibit inflammation. There are more skin accessory organs than OVA group, indicating that M cells can protect skin accessory organs. Atopic dermatitis has a very good therapeutic effect.
  • the drug combination can relieve rash erythema, reduce atopic dermatitis phenotype, reduce AD-like skin lesions, reduce the thickness of the fat layer or/and reduce the thickness of the stratum corneum.
  • the drug combination can reduce the degree of itching, protect the accessory organs of the skin, reduce the proliferation of mast cells, mediate the imbalance of Th1/Th2 cells, reduce the intensity of IgE expression in CD19-positive cells, improve allergic diseases, and/or Inhibit inflammation.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like.
  • the administration is subcutaneous injection or subcutaneous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological carrier or pharmaceutically acceptable biological material, including but not limited to collagen scaffold, Matrigel, skin repair membrane, aminated gelatin, chitosan, silk fibroin, Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the drug combination also includes biological antibodies (such as but not limited to dupiluzumab, omalizumab).
  • Burn generally refers to heat, including hydrothermal (water, soup, oil, etc.), steam, high-temperature gas, flame, hot metal liquid or solid (such as molten steel, steel ingot) caused by tissue damage, mainly refers to the skin and/or mucous membrane In severe cases, it can also damage the subcutaneous or/and submucosal tissues, such as muscles, bones, joints and even internal organs. Scald is a kind of tissue damage caused by hot liquid, steam, etc., which is a kind of thermal burn.
  • Scald tissue damage caused by flameless high-temperature liquid (boiling water, hot oil, molten steel), high-temperature solid (hot metal, etc.) or high-temperature steam.
  • Low-temperature scalds are common, which can also be called low-temperature scalds. It is burns caused by long-term skin contact with low-heat objects higher than body temperature.
  • burn patients have limited skin and secondary damage to skin removal.
  • Wound infections lead to various complications such as difficulty in healing wounds and septic shock, the progressive deepening of infected necrotic wounds, and scar healing after wound healing causes contracture deformities, resulting in unsightly appearance and functional obstacles.
  • the patient has a poor prognosis and poor functional recovery.
  • Post-rehabilitation treatment has increased the patient’s psychological burden and economic burden. Therefore, it is necessary to find a method that can promote wound healing faster and better restore the appearance and function of the skin. solved problem.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of burns or scalds in a subject, or in the preparation of Use in a medicine for preventing and/or treating burns or scalds in a subject.
  • the pharmaceutical composition can be used to solve the problems of no functional recovery after skin injury, limited sources of skin grafts, and limited autologous skin.
  • the pharmaceutical composition can rebuild accessory organs after skin injury, accelerate wound healing, reduce fibrosis, etc., so as to restore skin function, reduce wound area, treat skin damage, and protect skin.
  • the pharmaceutical composition can reduce inflammation at the wound site after scald, and inhibit inflammation.
  • the pharmaceutical composition can promote vascular regeneration of skin wounds.
  • the pharmaceutical composition can promote hair follicle regeneration and increase factors such as ⁇ -Catenin, CD133, and Ki67.
  • the pharmaceutical composition can reduce collagen deposition and treat skin damage.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the culture supernatant of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like.
  • the surface application, drug combination is by surface transplantation or injection or surface spraying.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Refractory skin breakage is a phenomenon of skin breakage caused by various diseases or injuries. It is manifested as the skin is prone to repeated rupture, partial loss of skin function, and prone to scarring and other skin hyperplasia tissues. Common factors that cause intractable skin breakage include burns and scalds, diabetes (causing diabetic feet), lupus erythematosus, and psoriasis.
  • Diabetic foot The main symptoms of diabetic foot disease are lower limb pain and skin ulcers. Diabetic foot ulcers and gangrene are the main reasons leading to clinical non-traumatic amputation, and they also seriously endanger the labor ability and quality of life of diabetic patients. Sugarfoot is usually the result of lower extremity neuropathy, vascular disease, and infection.
  • Diabetic nephropathy 1. Diabetic nephropathy
  • Diabetic retinopathy is the most important manifestation of diabetic microangiopathy, a fundus disease with specific changes, and one of the serious complications of diabetes. Clinically, based on whether there is retinal neovascularization as a sign, diabetic retinopathy without retinal neovascularization is called non-proliferative diabetic retinopathy (or simple or background type), and diabetes with retinal neovascularization will occur Retinopathy is called proliferative diabetic retinopathy.
  • Diabetes-related uveitis generally has the following 4 conditions: 1Uveitis related to diabetes itself; 2Infectious uveitis, the chance of endogenous infectious endophthalmitis in diabetic patients is relatively normal The number of people has increased significantly; 3With some specific types of uveitis, but the two are accidental coincidence, or there is an internal connection; 4Infective endophthalmitis or aseptic endophthalmitis after intraocular surgery. It mostly occurs in middle-aged and elderly diabetic patients.
  • Diabetic cataract occurs in juvenile diabetic patients whose blood sugar is not well controlled. Most of the disease occurs in both eyes, which develops rapidly, and can even develop into complete turbidity within a few days, weeks, or months.
  • the foot is a complex target organ of diabetes, a multi-system disease. Diabetes patients due to peripheral neuropathy and peripheral vascular disease combined with excessive mechanical pressure, can cause the destruction and deformity of the soft tissue and bone and joint system of the foot, which can lead to a series of foot problems, from mild neurological symptoms to severe ulcers , Infection, vascular disease, Charcot arthropathy and neuropathic fractures. In fact, similar pathological changes can also occur on the upper limbs, face and trunk, but the incidence of diabetic foot is significantly higher than other parts.
  • Coronary heart disease is a major macrovascular complication of diabetes. Studies have shown that the risk of death from coronary heart disease in diabetic patients is 3 to 5 times higher than that of non-diabetic patients.
  • the pathological mechanism is atherosclerosis. Hyperglycemia, high systolic blood pressure, high cholesterol, increased low-density lipoprotein, decreased high-density lipoprotein, age, sex, smoking, and family history are all risk factors for its onset.
  • cerebrovascular disease mainly manifested as cerebral arteriosclerosis, ischemic cerebrovascular disease, and cerebral hemorrhage , Brain atrophy, etc., is one of the main causes of death in diabetic patients.
  • diabetic neuropathy chronic distal symmetric sensorimotor polyneuropathy, that is, diabetic peripheral neuropathy.
  • the incidence is very high.
  • Unfortunately In terms of treatment, especially in the eradication of diabetic neuropathy, it is quite difficult, so the focus is on preventing its occurrence and controlling its development.
  • Intractable skin breakage is not a disease, but a phenomenon of skin breakage caused by multiple diseases or injuries. It is manifested as the skin is prone to repeated rupture, partial loss of skin function, and proliferation of skin tissues such as scars. Common factors that cause intractable skin breakage include burns and scalds, diabetes, lupus erythematosus, and psoriasis. At present, there is no complete solution to these problems, because such damage is often accompanied by complex immune disorders and tissue regeneration disorders, and a single treatment plan cannot solve all problems.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of refractory skin in a subject, or in the preparation of It is used to prevent refractory skin in subjects, or delay or reduce scleroderma or prevent scleroderma, or alleviate the symptoms of refractory skin.
  • the refractory skin is derived from these factors (such as but not limited to burns and scalds, diabetes, lupus erythematosus, psoriasis, etc.)
  • the administration can be by subcutaneous injection.
  • the drug combination can improve the healing speed of wounds, reduce the wound area, promote the regeneration of blood vessels in skin wounds, and regenerate the skin after injury.
  • the drug combination can reduce the expression of CD3, F4/80, MPO genes or proteins in the treatment of refractory skin, and inhibit inflammation.
  • the drug combination can increase the expression of ⁇ -Catenin, CD133, Ki67, and CD31 genes or proteins in the treatment of refractory skin.
  • the drug combination can promote hair follicle regeneration.
  • the drug combination can reduce the expression of pro-inflammatory factors IL-1 ⁇ , IL-6 and TNF ⁇ in diabetic nephropathy, can reduce the thickening of the glomerular membrane and the infiltration of macrophages, and reduce the incidence of diabetes.
  • the renal glomerulopathy increases the weight of the rat’s kidney, kidney and body mass index, so it can have a good therapeutic effect on diabetic nephropathy.
  • the drug combination can accelerate the healing of the diabetic foot, reduce the inflammation of the skin wound, promote the regeneration of blood vessels and hair follicles, reduce the deposition of collagen, and inhibit the occurrence of fibrosis in the diabetic foot. Effectively treat skin damage.
  • the drug combination can lower blood sugar and regulate inflammation in diabetic ocular complications, significantly reduce fasting blood glucose and HbA1c levels, and have certain improvements in visual function and macular edema. Trend, so it can be a good treatment for diabetic eye complications.
  • the drug combination can inhibit vascular calcification in diabetes complicated by vascular calcification, so as to have a good therapeutic effect on vascular calcification diseases in complications.
  • the drug combination can enhance the ability of astrocytes to resist oxidative stress in diabetic neuropathy, and enhance their ability to clear glutamate in the brain and maintain K+ balance in the brain, thereby Promote neuronal function, brain balance and synapse formation, and improve cognitive impairment caused by diabetes.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration can be by subcutaneous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Psoriasis is a common chronic inflammatory skin disease with the characteristics of refractory and recurrent. The cause of the disease is unknown. It is currently believed to be a disease caused by the interaction of genetic factors and environmental factors.
  • common type pustular type
  • joint type erythroderma
  • erythroderma The skin lesions are characterized by the appearance of erythema papules at first, covered with layers of silvery white scales, dry skin, desquamation and scabs, and some skin symptoms are continuous, like a map, some are itching, pus and water, blood stains, unbearable .
  • Psoriasis vulgaris the manifestation is very obvious, is red papules caused by dermatitis. It is the size of a mung bean, and then slowly grows to form silvery white dry scales. If the situation is more serious, large white scales will cover the whole body and look particularly scary. It may even be accompanied by bleeding, which is unacceptable.
  • Pustular type There are very dense water pustules with uneven sizes. As the condition worsens, the pustules will continue to grow, and finally form erythema. This symptom is an emergency, and it bursts out suddenly. Suffering from this type of psoriasis, the patient will feel fever, joint pain and swelling.
  • Erythroderma-type psoriasis manifested as diffuse flushing, infiltration and swelling of the skin throughout the body, accompanied by a large number of bran-like scales, during which there may be flaky normal skin, and may be accompanied by systemic symptoms such as fever and superficial lymphadenopathy. The course of the disease is long and it is easy to relapse.
  • joint disease In addition to skin lesions, joint disease can occur. Any joint may be affected, including the elbow and knee joints, the small joints of the fingers and toes, the spine and the sacroiliac joints. It can be manifested as joint swelling and pain, restricted movement, joint deformity in severe cases, and progressive development, but the rheumatoid factor test is often negative.
  • Psoriasis (commonly known as psoriasis) is a well-known skin disease. Once it occurs, red papules or plaques may appear on the skin, and it is covered with multiple layers of silvery white scales. It usually occurs on the limbs, head and back, and even affects the whole body. Some cases never heal for almost a lifetime. There is currently no specific treatment. The incidence of this disease is mainly young and middle-aged, which has a greater impact on the physical health and mental status of patients, and has caused a huge burden on the society and economy. Epidemiological surveys show that there are currently about 6.5 million psoriasis patients in my country, with an incidence rate of 0.47%.
  • psoriasis is considered to be an autoimmune skin disease caused by dendritic cells (DC) and T lymphocytes, innate immunity and adaptive immunity, and interaction between genetic background and environmental factors. Excessive proliferation of keratinocytes caused by inflammation, and other characteristic lesions of psoriasis.
  • Targeted antagonistic biologics for the key cytokines (TNF- ⁇ , IL-12, IL-23, IL-17) in the pathogenesis of psoriasis are extremely effective in clinical treatment, but the high cost required for long-term maintenance treatment As well as potential serious adverse reactions, the wide application of this type of biological agents is limited.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of psoriasis in a subject, or in the preparation of To prevent psoriasis in subjects, or delay or reduce psoriasis or prevent psoriasis from alleviating.
  • the drug combination can relieve rashes, erythema, scale, infiltration, reduce psoriatic dermatitis phenotype, reduce psoriatic skin lesions, reduce epidermal spinous layer or reduce stratum corneum thickness.
  • the drug combination can reduce ROS levels, reduce the recruitment of splenic neutrophils and dendritic cells, reduce inflammatory infiltrating cells, or/and regulate immune function.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred protocols, administration is via back or intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Immune system diseases refer to pathological reactions caused by damage to the immune system. Mainly include: infectious diseases, hypersensitivity diseases, autoimmune diseases, immunoproliferative diseases, immunodeficiency diseases and immune-related diseases.
  • autoimmune disease refers to a disease in which the body's immune system functions abnormally, which causes the body to attack its own tissues. Common autoimmune diseases often involve multiple systems and organs (such as skin, bones, muscles, internal organs, etc.), thereby forming systemic autoimmune diseases.
  • erythematosus Including systemic lupus erythematosus, mandatory spondylitis, rheumatoid arthritis, psoriasis, erythroderma, glomerulonephritis, Anka-related vasculitis, scleroderma, primary systemic amyloidosis, Autoimmune hepatitis, autoimmune pancreatitis, autoimmune gastritis, Crohn's disease, ulcerative colitis, erythema nodosum, Hashimoto's thyroiditis, alopecia areata, eczema type 1 diabetes.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for the prevention, treatment, delay and/or alleviation of autoimmune diseases; or, the present invention provides The method for preventing, treating, delaying and/or reducing autoimmune diseases includes administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the autoimmune disease is selected from scleroderma, lupus erythematosus (such as systemic lupus erythematosus), psoriasis, rheumatoid arthritis, dermatomyositis, multiple sclerosis, myasthenia gravis , Polymyositis, inflammatory bowel disease (for example, ulcerative colitis (UC), Crohn's disease (CD)), Sjogren syndrome, vasculitis (for example, systemic vasculitis) , Adult Still's disease or any combination thereof.
  • scleroderma lupus erythematosus (such as systemic lupus erythematosus), psoriasis, rheumatoid arthritis, dermatomyositis, multiple sclerosis, myasthenia gravis , Polymyositis, inflammatory bowel disease (for example, ulcerative colitis (UC), Crohn's disease (CD
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from anti-inflammatory drugs or immunosuppressive agents.
  • the additional active ingredient is selected from non-steroidal anti-inflammatory drugs (such as ibuprofen, diclofenac, naproxen, indomethacin, piroxicam, meloxicam, nabumetone Or Nimesulide), steroidal anti-inflammatory drugs (such as prednisone, dexamethasone or hydrocortisone), antibodies or antagonists of inflammatory cytokines (for example, TNF ⁇ , IL-1, IL-6 , IL-8, GM-CSF or PAF antibody or receptor antagonist), anti-inflammatory cytokines (such as IL-10, IL-4, IL-11, IL-13 or TGF ⁇ ), anti-proliferative/antimetabolites Drugs (such as cyclophosphamide, methotrexate, azathioprine, leflunomide), calcineurin inhibitors (such as cyclosporine, tac), calcineurin inhibitor
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 No less than 5 ⁇ 10 4 , no less than 7 ⁇ 10 4 , no less than 1 ⁇ 10 5 , no less than 3 ⁇ 10 5 , no less than 5 ⁇ 10 5 , no less 7 ⁇ 10 5 pieces, not less than 1 ⁇ 10 6 pieces, not less than 3 ⁇ 10 6 pieces, not less than 5 ⁇ 10 6 pieces, not less than 7 ⁇ 10 6 pieces, not less than 1 ⁇ 10 7 pieces , Not less than 3 ⁇ 10 7 pieces, not less than 5 ⁇ 10 7 pieces, not less than 7 ⁇ 10 7 pieces, not less than 1 ⁇ 10 8 pieces, not less than 3 ⁇ 10 8 pieces, not less than 5 ⁇ 10 8 pieces, not less than 7 ⁇ 10 8 pieces, not less than 1 ⁇ 10 9 pieces, not less than 3 ⁇ 10 9 pieces, not less than 5 ⁇ 10 9 pieces, not less than 7 ⁇ 10 9 pieces, Not less than 1 ⁇ 10 4 (for example
  • the unit dose of the drug contains 1 ⁇ 10 5 to 1 ⁇ 10 8 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the present invention also provides a product for preventing, treating, delaying and/or reducing autoimmune diseases, which contains the mesenchymal stem cell population of the present invention.
  • the product further contains an additional active ingredient, and the additional active ingredient is as defined above.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the product is an injection, a microinjection, a mucosal patch, an enema, a suppository, a gel, an oral agent, an aerosol, a drop, an ointment, an embedding agent, or a capsule.
  • the product is an implant.
  • Lupus erythematosus is a typical autoimmune connective tissue disease, which is more common in women aged 15-40.
  • Lupus erythematosus is a disease spectrum disease, which can be divided into discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), systemic lupus erythematosus (SLE), deep-seated lupus erythematosus (LEP), neonates Subtypes such as lupus erythematosus (NLE) and drug-induced lupus erythematosus (DIL).
  • DLE discoid lupus erythematosus
  • SCLE subacute cutaneous lupus erythematosus
  • SLE systemic lupus erythematosus
  • LEP deep-seated lupus erythematosus
  • NLE drug-induced lupus
  • systemic lupus erythematosus refers to an autoimmune disease with slow onset, insidious occurrence, diverse clinical manifestations and various changes.
  • An autoimmune disease involving many systems and organs, due to cellular and humoral immune functions Obstacles, producing a variety of autoantibodies. It can affect the skin, serosal membranes, joints, kidneys and central nervous system, and is characterized by autoimmunity.
  • autoantibodies There are many kinds of autoantibodies in the patient's body, which not only affect humoral immunity, but also affect cellular immunity, and the complement system also has changes.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicament for the prevention, treatment, delay and/or alleviation of lupus erythematosus (such as systemic lupus erythematosus);
  • the present invention provides a method for preventing, treating, delaying and/or alleviating lupus erythematosus (such as systemic lupus erythematosus), which comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchyme Stem cell population or its culture supernatant.
  • the mesenchymal stem cell population of the present invention can slow down the pathogenesis of the system by reducing anti-double-stranded DNA antibodies.
  • the mesenchymal stem cell population of the present invention can slow down the pathogenesis of lupus erythematosus by avoiding or preventing or inhibiting spleen and nape lymphatic enlargement.
  • the mesenchymal stem cell population of the present invention can promote the formation of glomeruli.
  • the mesenchymal stem cell population of the present invention is capable of inhibiting pro-inflammatory factors.
  • the mesenchymal stem cell population of the present invention can reduce the number of T cell populations in the spleen (eg, CD3 + T cells, CD4 + T cells, and CD4 + T cells).
  • T cell populations in the spleen eg, CD3 + T cells, CD4 + T cells, and CD4 + T cells.
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from anti-inflammatory drugs or immunosuppressive agents.
  • the additional active ingredient is selected from non-steroidal anti-inflammatory drugs (such as ibuprofen, diclofenac, naproxen, indomethacin, piroxicam, meloxicam, nabumetone Or Nimesulide), steroidal anti-inflammatory drugs (such as prednisone, dexamethasone or hydrocortisone), antibodies or antagonists of inflammatory cytokines (for example, TNF ⁇ , IL-1, IL-6 , IL-8, GM-CSF or PAF antibody or receptor antagonist), anti-inflammatory cytokines (such as IL-10, IL-4, IL-11, IL-13 or TGF ⁇ ), anti-proliferative/antimetabolites Drugs (such as cyclophosphamide, methotrexate, azathioprine, leflunomide), calcineurin inhibitors (such as cyclosporine, tac), calcineurin inhibitor
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 No less than 5 ⁇ 10 4 , no less than 7 ⁇ 10 4 , no less than 1 ⁇ 10 5 , no less than 3 ⁇ 10 5 , no less than 5 ⁇ 10 5 , no less 7 ⁇ 10 5 pieces, not less than 1 ⁇ 10 6 pieces, not less than 3 ⁇ 10 6 pieces, not less than 5 ⁇ 10 6 pieces, not less than 7 ⁇ 10 6 pieces, not less than 1 ⁇ 10 7 pieces , Not less than 3 ⁇ 10 7 pieces, not less than 5 ⁇ 10 7 pieces, not less than 7 ⁇ 10 7 pieces, not less than 1 ⁇ 10 8 pieces, not less than 3 ⁇ 10 8 pieces, not less than 5 ⁇ 10 8 pieces, not less than 7 ⁇ 10 8 pieces, not less than 1 ⁇ 10 9 pieces, not less than 3 ⁇ 10 9 pieces, not less than 5 ⁇ 10 9 pieces, not less than 7 ⁇ 10 9 pieces, Not less than 1 ⁇ 10 4 (for example
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the skin is the organ with the largest surface area of the human body. It is a key structure that protects internal tissues from mechanical damage, microbial infection, ultraviolet radiation and extreme temperature effects.
  • Skin system diseases include viral skin diseases, bacterial skin diseases, fungal skin diseases, animal skin diseases, physical skin diseases, dermatitis, eczema, drug eruptions, urticaria skin diseases, itchy skin diseases, erythema and scaly skin Disease, connective tissue disease, bullous skin disease, vasculitis skin disease, skin accessory organ disease, pigmented skin disease, hereditary skin disease, skin tumor, sexually transmitted disease.
  • Scleroderma is a type of connective tissue disease of the skin.
  • Scleroderma or systemic sclerosis (SSC) is a progressive, debilitating autoimmune disease characterized in that skin fibroblasts deposit excess protein in the extracellular matrix, also known as skin fibrosis.
  • Typical skin lesions go through three stages in sequence: swelling, infiltration, and atrophy. The lesions are symmetrical. Most of the lesions gradually extend from the fingers to the proximal end, and involve the connective tissues of internal organs such as the heart, lungs, kidneys, and digestive tract. disease.
  • Scleroderma is an autoimmune disease characterized by thickening of the skin and localized or diffuse fibrosis. It can affect organs such as the lungs, kidneys, liver, and heart. The pathogenesis is unknown. Current studies have found that the disease mainly involves three aspects: small vessel disease, fibrosis caused by excessive accumulation of extracellular matrix, and immune abnormality. Inflammatory cell infiltration is the main feature of the early stage of scleroderma. T lymphocyte infiltration is the main feature. Studies have shown that T lymphocytes can release a variety of cytokines, cause inflammation and vascular disease, activate fibroblasts and promote collagen fibers. synthesis. At present, immunosuppressants and symptomatic treatments are mainly used for scleroderma, but the therapeutic effect is not ideal, and there are many adverse reactions. It is necessary to find more effective treatment methods.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicament for the prevention, treatment, delay and/or alleviation of scleroderma; or, the present invention provides prevention , A method for treating, delaying and/or alleviating scleroderma, which comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the mesenchymal stem cell population can significantly thin the dermal layer of the skin in scleroderma and reduce the accumulation of collagen fibers.
  • the mesenchymal stem cell population can reduce the occurrence of hardening and thickening of the skin in scleroderma, and play an effective therapeutic effect on scleroderma.
  • the mesenchymal stem cell population can increase the number of hair follicles and reduce the thickness of the dermis in scleroderma.
  • the mesenchymal stem cell population can prevent significant thinning of the fat layer in scleroderma and prevent the reduction of skin appendages.
  • the mesenchymal stem cell population can inhibit inflammatory factors (such as IL-17, IL-6, TNF), inhibit the expression level of inflammatory factors, or/and increase the inhibition of inflammation in scleroderma Factor expression level (such as IL10), increase MMP1 protein expression level, reduce or inhibit smooth muscle actin (a-SMA) expression.
  • inflammatory factors such as IL-17, IL-6, TNF
  • IL-10 scleroderma Factor expression level
  • MMP1 protein expression level such as IL10
  • a-SMA smooth muscle actin
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration can be by subcutaneous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the additional active ingredient is selected from anti-inflammatory drugs or immunosuppressive agents.
  • the additional active ingredient is selected from non-steroidal anti-inflammatory drugs (such as ibuprofen, diclofenac, naproxen, indomethacin, piroxicam, meloxicam, nabumetone Or Nimesulide), steroidal anti-inflammatory drugs (such as prednisone, dexamethasone or hydrocortisone), antibodies or antagonists of inflammatory cytokines (for example, TNF ⁇ , IL-1, IL-6 , IL-8, GM-CSF or PAF antibody or receptor antagonist), anti-inflammatory cytokines (such as IL-10, IL-4, IL-11, IL-13 or TGF ⁇ ), anti-proliferative/antimetabolites Drugs (such as cyclophosphamide, methotrexate, azathioprine, leflunomide), calcineurin inhibitors (such as cyclosporine, tac), calcineurin inhibitor
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 5 (for example, not less than 1 ⁇ 10 5 , not less than 5 ⁇ 10 5).
  • the unit dose of the drug contains not less than 1 ⁇ 10 5 (for example, not less than 1 ⁇ 10 5 , not less than 5 ⁇ 10 5).
  • the unit dose of the drug contains 1 ⁇ 10 5 to 1 ⁇ 10 8 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for the prevention and/or treatment of respiratory diseases; or, the present invention provides prevention and/or treatment
  • the method for respiratory diseases includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or the culture supernatant thereof to a subject in need thereof.
  • Respiratory System is the general term for a series of organs that the human body exchanges gas with the outside air, including the nose, pharynx, larynx, trachea, bronchus, lungs composed of a large number of alveoli, blood vessels, lymphatic vessels, nerves, and pleura, etc. organization.
  • the nose, pharynx, and larynx are often referred to as the upper respiratory tract, and the gas passage below the trachea (including the bronchi at all levels in the lungs) is called the lower respiratory tract.
  • Lung disease refers to the disease of the lung itself or the pulmonary manifestations of systemic disease. Mainly include infectious lung diseases, lung diseases related to air pollution and smoking, occupation-related lung diseases, immune-related lung diseases, genetic-related lung diseases, and lung diseases of unknown cause.
  • the lung disease is selected from pulmonary vascular disease, idiopathic pulmonary fibrosis, acute respiratory distress, pneumoconiosis, and pneumonia.
  • the pulmonary vascular disease is selected from pulmonary hypertension, pulmonary heart disease, pulmonary embolism, pulmonary vasculitis, chronic obstructive pulmonary disease, and pulmonary interstitial disease.
  • the lung disease is pulmonary hypertension (PAH).
  • Hazardous dust includes silica (ie quartz), silicate, coal, iron, and tin.
  • Smoke includes harmful gases such as sulfur dioxide, nitrogen dioxide, ammonium, hydrochloric acid, chlorine, phosgene, and strong acid fumes.
  • Toxic substances include uranium, nickel, chromate, asbestos, dichloromethyl ether, etc.
  • Pneumoconiosis is a systemic disease mainly caused by diffuse fibrosis (scarring) of lung tissue caused by long-term inhalation of productive dust (dust) during occupational activities and retention in the lungs.
  • Pneumoconiosis can be divided into inorganic pneumoconiosis and organic pneumoconiosis according to the type of dust inhaled.
  • Pneumoconiosis caused by inhalation of inorganic dust during production is called inorganic pneumoconiosis.
  • Most of the pneumoconiosis is inorganic pneumoconiosis.
  • Pneumoconiosis caused by inhalation of organic dust is called organic pneumoconiosis, such as cotton pneumoconiosis and peasant lungs.
  • Pneumoconiosis is a progressive chronic disease. It is not like acute infectious diseases or other chronic diseases (such as tuberculosis, hypertension, diabetes, etc.) that can see obvious therapeutic effects in a short period of time. It generally requires long-term treatment for several years. Obtain obvious curative effect.
  • the present invention relates to the preparation of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for preventing and/or treating pneumoconiosis, or delaying, or reducing pneumoconiosis, or preventing alleviation of pneumoconiosis
  • the present invention relates to a method for preventing and/or treating pneumoconiosis, or delaying, or reducing pneumoconiosis, or preventing pneumoconiosis, which comprises administering an effective amount of pneumoconiosis as described herein to a subject in need
  • the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition is administered to a subject in need.
  • the medicament of the present invention can reduce the level of inflammatory factors in the serum, improve lung function, reduce the area of dense lungs, and/or reduce the formation of fibrosis.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the drug of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Pneumonia refers to the infectious inflammation of the alveoli, remote airways and lung interstitium, which can be caused by infection by bacteria, viruses, and other pathogens. Among them, bacterial and viral pneumonia are the most common. Broadly speaking, pneumonia can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, allergies, and drugs. Patients often have typical symptoms such as fever, cough, and difficulty breathing.
  • Emphysema refers to a pathological condition in which the airway at the distal end of the terminal bronchiole has decreased in elasticity, over-inflated, inflated, and increased lung volume, or accompanied by damage to the airway wall. According to its cause, there are several types of emphysema: senile emphysema, compensated emphysema, interstitial emphysema, focal emphysema, paraseptal emphysema, obstructive pulmonary air swollen.
  • Bronchitis refers to chronic non-specific inflammation of the trachea, bronchial mucosa and surrounding tissues.
  • the main cause of bronchitis is chronic non-specific inflammation of the bronchus caused by repeated infections of viruses and bacteria.
  • Mainly include acute bronchitis and chronic bronchitis.
  • Chronic bronchitis is a chronic non-specific inflammation of the trachea, bronchial mucosa and surrounding tissues.
  • the main symptoms are cough, sputum, or wheezing.
  • Chronic obstructive pulmonary disease is a kind of chronic bronchitis and/or emphysema with the characteristics of airflow obstruction, which can further develop into common chronic diseases of pulmonary heart disease and respiratory failure. It is related to the abnormal inflammatory reaction of harmful gases and harmful particles, and the disability rate and fatality rate are very high.
  • the present invention relates to mesenchymal stem cell populations, cultures, culture supernatants or pharmaceutical compositions as described herein in preparation for the prevention and/or treatment of chronic pulmonary obstruction, or to delay or reduce chronic pulmonary obstruction, Or prevent the use of drugs for reducing chronic pulmonary obstruction; or, the present invention relates to methods for preventing and/or treating chronic pulmonary obstruction, or delaying or reducing chronic pulmonary obstruction, or preventing chronic pulmonary obstruction, including methods for reducing chronic pulmonary obstruction. Of subjects are administered an effective amount of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein.
  • the drug can reduce the area of dense lungs and improve lung function, including vital capacity, improve maximum ventilation, reduce airway resistance, reduce the average intercept of alveoli, maintain the structural integrity of the lungs, or/ And increase the partial pressure of oxygen in arterial blood.
  • the drug can reduce the level of pro-inflammatory factors, increase the level of anti-inflammatory factors, and inhibit inflammation.
  • the drug can reduce the expression of Collagen I and ⁇ -SMA protein in the lungs, and can inhibit the occurrence of fibrosis.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the drug of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration, and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection, lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Immune-related lung diseases refer to protective immune and allergic reactions in the lungs when the lungs are attacked by external allergens. Mainly manifested as acute, subacute or chronic interstitial pneumonia.
  • Infectious lung refers to diseases caused by pathogenic microorganisms infecting the lungs. Mainly divided into bacterial pneumonia, viral pneumonia, mycoplasma pneumonia, fungal pneumonia and tuberculosis.
  • Bacterial pneumonia is pneumonia caused by bacterial infection, including pneumonia caused by Streptococcus pneumoniae, Staphylococcus aureus, Gram-negative bacilli and other infections.
  • Viral pneumonia is pneumonia caused by upper respiratory virus infection, mainly including influenza virus, parainfluenza virus, cytomegalovirus, adenovirus, rhinovirus, coronavirus (SARS virus, MERS virus and new coronavirus) and some Influenza, pharyngitis, atypical pneumonia (SARS), Middle East respiratory syndrome (MERS) and new coronary pneumonia (COVID-19) caused by enteroviruses.
  • Mycoplasma pneumonia is pneumonia caused by Mycoplasma pneumoniae.
  • Fungal pneumonia includes pneumonia caused by fungi such as Aspergillus.
  • Pulmonary tuberculosis is a lung disease caused by Mycobacterium tuberculosis infection.
  • Acute respiratory failure is due to respiratory diseases, such as severe respiratory infection, acute respiratory obstructive disease, severe or critical asthma, acute pulmonary edema caused by various causes, pulmonary vascular disease, thoracic trauma or surgical injury, spontaneous pneumothorax and acute Increased pleural effusion leads to pulmonary ventilation and/or ventilation dysfunction, acute intracranial infection, brain trauma, cerebrovascular disease, etc. directly or indirectly inhibit the respiratory center, polio, myasthenia gravis, organophosphate poisoning, and cervical spine trauma, etc. Damage to the neuromuscular conduction system, causing insufficient ventilation and leading to acute respiratory failure.
  • respiratory diseases such as severe respiratory infection, acute respiratory obstructive disease, severe or critical asthma, acute pulmonary edema caused by various causes, pulmonary vascular disease, thoracic trauma or surgical injury, spontaneous pneumothorax and acute Increased pleural effusion leads to pulmonary ventilation and/or ventilation dysfunction, acute intracranial infection, brain trauma, cerebrovascular disease, etc. directly or indirectly inhibit the respiratory center,
  • ARDS Respiratory Distress Syndrome
  • Respiratory distress syndrome includes acute respiratory distress syndrome and neonatal respiratory distress syndrome.
  • COVID-19 caused by the new type of coronavirus “SARS-CoV-2” infection has a long incubation period, is highly infectious and harmful.
  • SARS-CoV-2 coronavirus
  • ARDS acute Respiratory Distress Syndrome
  • ARDS acute Respiratory Distress Syndrome
  • the current treatment plan for ARDS is limited to basic medical care and supportive ventilation strategies and other symptomatic treatments, and it is still unable to reverse the disease process, improve the quality of life of patients, and reduce the mortality rate.
  • Mechanical ventilation is the main treatment for patients with acute respiratory distress syndrome.
  • Drug treatments include: corticosteroids, statins, aspirin, ⁇ -2 receptor agonists, surfactants, and inhaled NO, etc., all of which have not shown significant efficacy.
  • auxiliary methods such as blood purification treatment, nutritional intervention, and fluid control, cannot meet the treatment of ARDS caused by COVID-19.
  • the present invention relates to mesenchymal stem cell populations, cultures, culture supernatants or pharmaceutical compositions as described herein in preparation for the prevention and/or treatment of respiratory distress syndrome, or to delay or reduce respiratory distress syndrome. Or prevent the use of drugs for alleviating respiratory distress syndrome; or, the present invention relates to a method for preventing and/or treating respiratory distress syndrome, or delaying or reducing respiratory distress syndrome, or preventing alleviating respiratory distress syndrome, It includes administering an effective amount of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein to a subject in need thereof.
  • the drug can relieve asthma, promote better absorption at the lesion site, inhibit inflammation, and/or restore lung function.
  • the drug can reduce low pro-inflammatory cytokines (such as IL-1 ⁇ , IL-1 ⁇ , IL-5, IL-8, IL-25 and CXCL10/IP-10) and increase anti-inflammatory cells Factors (such as IL-1RA, RANTES) levels.
  • cytokines such as IL-1 ⁇ , IL-1 ⁇ , IL-5, IL-8, IL-25 and CXCL10/IP-10
  • anti-inflammatory cells Factors such as IL-1RA, RANTES
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. It is preferably administered by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Idiopathic interstitial pneumonia is also known as idiopathic pulmonary fibrosis.
  • Idiopathic refers to a group of unexplained progressive lower respiratory diseases. The pathological process is generally progressive Slow diffuse alveolitis and/or alveolar structural disorder will eventually lead to the destruction of alveolar structure, forming complete fibrosis and vesicular honeycomb lungs in the alveolar cavity.
  • IIPs are divided into main IIPs, rare IIPs and unclassified IIPs.
  • IIPs There are 6 main types of IIPs, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), respiratory bronchiolitis with interstitial lung disease (RB-ILD), and Squamous interstitial pneumonia (DIP), cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP).
  • IPF idiopathic pulmonary fibrosis
  • iNSIP idiopathic nonspecific interstitial pneumonia
  • RB-ILD respiratory bronchiolitis with interstitial lung disease
  • DIP Squamous interstitial pneumonia
  • COPD cryptogenic organizing pneumonia
  • AIP acute interstitial pneumonia
  • rare IIPs including idiopathic lymphocytic interstitial pneumonia (iLIP) and idiopathic pleural pulmonary parenchymal elastic fibrosis (iPPFE).
  • Idiopathic pulmonary fibrosis IPF
  • Idiopathic pulmonary fibrosis is a chronic and progressive lung disease characterized by pulmonary interstitial fibrosis. Its etiology is still unclear, and it is the most common of the major idiopathic interstitial pneumonias. One type of. The disease is more common in the elderly, and the incidence has been on the rise in recent years. However, the diagnosis of IPF is still a clinical problem. The onset of IPF is hidden, there is often no obvious clinical manifestations in the early stage, and imaging and lung function are not typical. Therefore, patients with IPF are often diagnosed after the development of the disease to the appearance of multiple complications. . However, there is currently no effective treatment plan for IPF. The lung function of patients continues to deteriorate as the disease progresses, and the median survival time is only 2-3 years.
  • the present invention relates to the preparation of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for preventing and/or treating idiopathic pulmonary fibrosis, or delaying or reducing idiopathic pulmonary fibrosis.
  • Idiopathic pulmonary fibrosis or the use of drugs for preventing and alleviating idiopathic pulmonary fibrosis; or, the present invention relates to preventing and/or treating idiopathic pulmonary fibrosis, or delaying or reducing idiopathic pulmonary fibrosis, Or a method for preventing alleviation of idiopathic pulmonary fibrosis, which comprises administering an effective amount of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein to a subject in need thereof.
  • the pharmaceutical composition can improve the absorption of lung lesions and reduce pulmonary fibrosis.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. It is preferably administered by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • Pulmonary vascular disease is congenital, inherited or acquired changes in the structure and/or function of the pulmonary circulation, including pulmonary artery, pulmonary vein, and pulmonary microvascular disease.
  • the main symptoms are primary or secondary lesions of pulmonary hypertension, and pulmonary venous obstructive disease.
  • the main reason is related to the interaction of genetic susceptibility and environmental factors.
  • Secondary pulmonary hypertension is related to pulmonary venous hypertension, chronic hypoxia, thrombosis or embolic disease, and can also directly involve pulmonary vascular disease.
  • Pulmonary hypertension Pulmonary hypertension (Pulmonary hypertension, PH):
  • Pulmonary hypertension refers to a hemodynamic and pathophysiological state in which the pulmonary artery pressure rises above a certain threshold, which can lead to right heart failure. It can be an independent disease, a complication, or a syndrome. Patients are accompanied by main symptoms such as weakness and dyspnea. Without treatment, the course of the disease progresses quickly, and often develops into right heart failure and leads to death. Its characteristics include pulmonary vascular remodeling, pulmonary vascular resistance (PVR) caused by vascular obstruction, increased pulmonary artery pressure, and right ventricular hypertrophy.
  • PVR pulmonary vascular resistance
  • pulmonary hypertension is divided into five categories: 1Arterial pulmonary hypertension; 2Pulmonary hypertension caused by left heart disease; 3Pulmonary hypertension caused by hypoxia and/or lung disease; 4Chronic thromboembolic pulmonary hypertension; 5Pulmonary hypertension caused by multiple mechanisms and/or unknown mechanisms.
  • the most effective treatment method is drug therapy, including three types of drugs, including prostacyclin, endothelin-1 receptor antagonist, and type 5 phosphodiesterase inhibitor.
  • drugs including prostacyclin, endothelin-1 receptor antagonist, and type 5 phosphodiesterase inhibitor.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein in the preparation of a medicament for preventing and/or treating pulmonary hypertension, delaying or reducing pulmonary hypertension
  • the present invention relates to a method for preventing and/or treating pulmonary hypertension, delaying or reducing pulmonary hypertension, which comprises administering to a subject in need thereof an effective amount of the mesenchymal stem cell population, culture, Culture supernatant or pharmaceutical composition.
  • the drug can reduce the systolic pressure of the right ventricle in the treatment of pulmonary hypertension.
  • the drug can inhibit the formation of pulmonary hypertension in the treatment of pulmonary hypertension, increase the acceleration time of pulmonary artery blood flow, reduce the ratio of the diameter of the right ventricle to the left ventricle, reduce the mean pulmonary artery pressure, and reduce the lungs of rats with pulmonary hypertension.
  • the drug can inhibit inflammation, increase the level of anti-inflammatory factors, and reduce the level of pro-inflammatory factors.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 , Not less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 and not less than 1 ⁇ 10 7 , Not less than 3 ⁇ 10 7 pieces, not less than 5 ⁇ 10 7 pieces, not less than 7 ⁇ 10 7 pieces, not less than 1 ⁇ 10 8 pieces, not less than 3 ⁇ 10 8 pieces, not less than 5 ⁇ 10 8, less than 7 ⁇ 10 8 or no less than 1 ⁇ 10 9 or no less than 3 ⁇ 10 9 or no less than 5 ⁇ 10 9 or no less than 7 ⁇ 10 9 pieces, and Less than 1 ⁇ 10 4 (for example
  • the drug also contains other active ingredients, such as selected from the group consisting of prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase inhibitors; preferably, the The prostacyclin analog is selected from beraprost sodium, iloprost, epoprostol, treprostinil and any combination thereof; preferably, the endothelin receptor antagonist is selected from bosentan, ambrisentan , Maxitentan and any combination thereof; preferably, the phosphodiesterase inhibitor is selected from sildenafil, tadalafil, vardenafil, lioxigua and any combination thereof.
  • active ingredients such as selected from the group consisting of prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase inhibitors; preferably, the The prostacyclin analog is selected from beraprost sodium, iloprost, epoprostol, treprostinil and any combination thereof; preferably, the endothelin receptor antagonist is
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In some preferred embodiments, the administration can be by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the medicine also contains a pharmaceutically acceptable carrier or excipient; preferably, the carrier is selected from gelatin, chitosan, sodium alginate, collagen, silk protein, cellulose, fiber Protein, polylactic acid, polyurethane, polyethylene oxide, polyethylene glycol, polylactic acid glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix, decellularized scaffold and any combination thereof; preferably Preferably, the carrier is selected from gelatin, collagen, and any combination thereof; preferably, the drug is injection, microinjection, mucosal patch, enema, suppository, gel, oral agent, aerosol, drops,
  • the ointment, embedding agent or capsule is preferably an injection; preferably, the medicament further contains a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution, dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the administered dose is not less than 1 ⁇ 10 4 /time (for example, not less than 1 ⁇ 10 4 /time, not less than 3 ⁇ 10 4/time, not less than Less than 5 ⁇ 10 4 /time, not less than 7 ⁇ 10 4 /time, not less than 1*10 5 /time, not less than 3*10 5 /time, not less than 5*10 5 /Time, not less than 7*10 5 /time, not less than 1 ⁇ 10 6 /time, not less than 3 ⁇ 10 6 /time, not less than 5 ⁇ 10 6 /time, not less than 7 ⁇ 10 6 /time, not less than 1 ⁇ 10 7 /time, not less than 3 ⁇ 10 7 /time, not less than 5 ⁇ 10 7 /time, not less than 7 ⁇ 10 7 /time Times, not less than 1 ⁇ 10 8 /time, not less than 3 ⁇ 10 8 /time, not less than 5 ⁇ 10 8 /time, not less than 7 ⁇ 10 8 /time, not less than 1 ⁇ 10 9
  • a prophylactic and/or therapeutically effective amount of mesenchymal stem cell population is administered to a subject through the following routes: injection administration, mucosal administration, cavity administration, oral administration, respiratory administration Or skin administration.
  • the method further comprises simultaneously, sequentially or alternately administering to the subject a prophylactic and/or therapeutically effective amount of other active ingredients, for example selected from prostacyclin analogs, endothelin Receptor antagonist and phosphodiesterase inhibitor; preferably, the prostacyclin analog is selected from the group consisting of beraprost sodium, iloprost, epoprostol, treprostinil and any combination thereof; preferably, The endothelin receptor antagonist is selected from the group consisting of bosentan, ambrisentan, maxitentan and any combination thereof; preferably, the phosphodiesterase inhibitor is selected from sildenafil, tadalafil, Vardenafil, Leo Sigua and any combination thereof.
  • active ingredients for example selected from prostacyclin analogs, endothelin Receptor antagonist and phosphodiesterase inhibitor
  • the prostacyclin analog is selected from the group consisting of beraprost sodium, iloprost, epoprostol,
  • the present invention also provides a product for preventing, treating, delaying and/or alleviating respiratory diseases, which contains the mesenchymal stem cell population of the present invention.
  • the product further contains an additional active ingredient, and the additional active ingredient is as defined above.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the product is an injection, a microinjection, a mucosal patch, an enema, a suppository, a gel, an oral agent, an aerosol, a drop, an ointment, an embedding agent, or a capsule.
  • the product is an implant.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for the prevention and/or treatment of eye diseases; or, the present invention provides prevention and/or treatment
  • the method for ocular diseases includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or the culture supernatant thereof to a subject in need thereof.
  • Eye diseases are selected from ocular surface damage (such as corneal damage), dry eye, meibomian gland dysfunction (MGD), glaucoma, cataract, conjunctivitis, keratitis, blepharitis, stye, stye, retinopathy, retina Prolapse, fundus venous vascular disease, or any combination thereof.
  • ocular surface damage such as corneal damage
  • dry eye meibomian gland dysfunction (MGD)
  • MBD meibomian gland dysfunction
  • glaucoma cataract
  • conjunctivitis keratitis
  • blepharitis stye
  • stye stye
  • retinopathy retina Prolapse
  • fundus venous vascular disease or any combination thereof.
  • the medicament further comprises a carrier or excipient.
  • the carrier is selected from the group consisting of gelatin, chitosan, sodium alginate, collagen, silk protein, cellulose, fibrin, polylactic acid, polyurethane, polyethylene oxide, polyethylene glycol, poly Lactate glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix, decellularized scaffold, or any combination thereof.
  • the carrier is selected from gelatin, collagen, or any combination thereof.
  • the medicament further comprises a second active ingredient.
  • the second active ingredient is, for example, an antibacterial and anti-inflammatory drug.
  • the second active ingredient is selected from the group consisting of tetracycline hydrochloride eye drops, prednisone acetate eye ointment, hydrocortisone acetate eye drops, hydrocortisone acetate eye ointment, dexamethasone eye drops Liquid, polymyxin B eye drops, glutathione eye drops, erythromycin eye ointment, yellow mercuric oxide eye ointment, chlortetracycline eye ointment, atropine sulfate eye ointment, boric acid eye ointment or any combination thereof.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 , not less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 10 7 , not less than 3 ⁇ 10 7 , not less than 5 ⁇ 10 7 , Not less than 7 ⁇ 10 7 , not less than 1 ⁇ 10 8 , not less than 3 ⁇ 10 8 , not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 10 9 , no Less than 3 ⁇ 10 9 , not less than 5 ⁇ 10 9 , not less than 7 ⁇ 10 9 , not less than 1 ⁇ 10 9
  • the dose of mesenchymal stem cells is not less than 1 * 10 4 cells / mL (e.g. less than 1 ⁇ 10 4, less than 3 ⁇ 10 4, less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , Not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 10 7 , not less than 3 ⁇ 10 7 , not less than 5 ⁇ 10 7 , no Less than 7 ⁇ 10 7 , not less than 1 ⁇ 10 8 , not less than 3 ⁇ 10 8 , not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 10 9 , not less than 3 ⁇ 10 9 , not less than 5 ⁇ 10 9 , not less than 7 ⁇ 10 9 , not less than 1 ⁇ 10 10 10
  • the route of administration of the mesenchymal stem cells is selected from injection administration, smear administration, paste administration, enema administration, perfusion administration, rectal administration, and oral administration.
  • the method further comprises administering a second active ingredient to a subject in need thereof, the second active ingredient being as described or defined above.
  • the subject is a mammal, such as a human.
  • the present invention provides a product for treating eye diseases, which comprises a first active ingredient mesenchymal stem cell population.
  • the mesenchymal stem cell population is as described or defined previously.
  • the eye disease is as described or defined previously.
  • the product further comprises a second active ingredient.
  • the second active ingredient is as previously described or defined.
  • the first active ingredient and the second active ingredient are present alone or in combination.
  • the first active ingredient is administered in combination with a second active ingredient selected from the foregoing.
  • the product is an implant.
  • the implant is used to improve the microenvironment and suppress immune rejection.
  • the subject is a mammal, such as a human.
  • the ocular surface injury is selected from chemical burns of the eye (e.g. cornea) (e.g. alkali, acid burn), thermal burns of the eye (e.g. cornea), corneal injury, or any combination thereof.
  • chemical burns of the eye e.g. cornea
  • alkali, acid burn e.g. alkali, acid burn
  • thermal burns of the eye e.g. cornea
  • corneal injury or any combination thereof.
  • Ocular surface damage is one of the main causes of blindness worldwide. Among them, the most common causes are chemical burns of the eye (such as alkali and acid burns) and thermal burns. This type of damage can severely damage the ocular surface and is difficult to treat. , The prognosis is poor, often leading to blindness and even loss of eyeballs. Corneal alkali burn is the most serious of chemical burns. Alkaline substances can cause corneal tissue liquefaction and necrosis, causing serious damage to limbal stem cells. Severe loss of limbal stem cells can cause continuous inflammation, corneal and conjunctival epithelial metaplasia, neovascularization, and scarring of the corneal stroma. The subsequent immune inflammatory reaction is more likely to develop to the deep level, and cause corneal ulcers and perforations, secondary glaucoma and concurrent cataracts, which seriously damage the anatomical structure and visual function of the eye.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of ocular surface damage in a subject, or in preparation To prevent ocular surface damage in subjects, or delay or alleviate stroke or prevent ocular surface damage.
  • Corneal alkali burn is a kind of ocular surface damage.
  • the drug combination can treat corneal alkali, reduce corneal alkali burn, promote the recovery of corneal alkali damage, reduce inflammation, reduce the concentration of myeloperoxidase (MPO) in the cornea, and reduce the number of new blood vessels, Reduce the level of MMP-9, or/and reduce the levels of pro-inflammatory cytokines (IL-6 and IL-1 inhibitors) and chemokines (CXCL1/cinc1 and CCL2/MCP-1).
  • MPO myeloperoxidase
  • Cornea The transparent fibrous membrane of the blood vessels at the front of the eyeball wall, which is round and occupies one-sixth of the outer layer. It is mainly composed of avascular connective tissue; histologically, it is divided into five layers from front to back: epithelial cell layer, Front elastic layer, matrix layer, back elastic layer and endothelial cell layer.
  • the cornea is highly transparent, the surface is smooth, the front is convex and the back is concave, shaped like a convex-concave lens, curved like a spherical surface and has a refractive effect.
  • Corneal alkali burn After the solution, dust or gas of alkaline substance comes into contact with the cornea, it causes the dissolution of fat and protein, the destruction of the tissue, and the continued diffusion of the alkaline substance and the penetration into the deep tissues, which causes the decomposition and necrosis of the corneal tissue cells, which mostly occurs in the chemical industry. Factory, laboratory or construction site.
  • Keratitis is inflammation caused by the invasion of corneal tissue by exogenous or endogenous pathogenic factors when the defense ability of the cornea is weakened.
  • the main manifestations of patients are eye pain, photophobia, tearing, blepharospasm and other ocular irritation. Keratitis is generally limited to part of the cornea in the early stage, and can progress gradually without effective treatment, and can cause irreversible visual damage in the late stage. Infectious keratitis mostly occurs in the central area of the cornea, while immune keratopathy easily occurs in the periphery of the cornea.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like.
  • the administration is by corneal injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological scaffolds or pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry or mixture
  • Movement system diseases refer to diseases that occur in bones, joints, muscles, ligaments and other parts, and are common clinically. Can be manifested as a local disease can also be manifested as a systemic disease. Local cases such as trauma, fracture, dislocation, deformity, etc. Systemic diseases such as rheumatoid arthritis can occur in the hands, wrists, knees, and hips. Bone joint tuberculosis often occurs in the spine and hip joints. Many local lesions of the motor system are diagnosed and treated in orthopedics. Some systemic diseases of the motor system are diagnosed and treated in internal medicine, such as rheumatoid arthritis, and some are still diagnosed and treated in orthopedics, such as bone and joint tuberculosis.
  • Bone-related diseases include all diseases related to bones, joints, ligaments, cartilage, and structures that support the limbs, neck, and back. Related diseases are selected from cartilage sprains, strains and lacerations, arthritis, bursitis, acute and chronic back pain, osteoporosis, trigger finger, osteogenesis imperfecta and its comorbidities.
  • the present invention provides the use of the mesenchymal stem cell population or the culture supernatant thereof in the preparation of a medicament for the prevention, treatment, delay and/or alleviation of motor diseases or bone-related diseases; or,
  • the present invention provides a method for preventing, treating, delaying and/or alleviating motor system diseases or bone-related diseases, which comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its Culture the supernatant.
  • the motor system disease includes, for example, trauma (e.g., fracture, dislocation, soft tissue injury, etc.), or bone disease.
  • the bone-related disease is selected from cartilage sprains, strains and lacerations, arthritis, bursitis, acute and chronic back pain, osteoporosis, trigger finger, osteogenesis imperfecta And its comorbidities.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient.
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 , no Less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 10 7 , not less than 3 ⁇ 10 7 , not less than 5 ⁇ 10 7 , not less than 7 ⁇ 10 7 , not less than 1 ⁇ 10 8 , not less than 3 ⁇ 10 8 , not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 10 9 , Not less than 3 ⁇ 10 9 , not less than 5 ⁇ 10 9 , not less than 7 ⁇ 10 9 , not less than 1 ⁇ 10 9
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the present invention also provides a product for preventing, treating, delaying and/or alleviating motor system diseases or bone-related diseases, which contains the mesenchymal stem cell population of the present invention.
  • the product further contains an additional active ingredient, and the additional active ingredient is as defined above.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the product is an injection, a microinjection, a mucosal patch, an enema, a suppository, a gel, an oral agent, an aerosol, a drop, an ointment, an embedding agent, or a capsule.
  • the product is an implant.
  • Arthritis refers to any disease that affects the joints. Symptoms often include joint pain and stiffness. Other possible symptoms include redness, heat, swelling, and reduced range of motion of the diseased joint. Certain arthritis, in addition to joints, can also affect other organs. The onset may be gradual or sudden and acute. There are more than 100 types of arthritis, the most common being osteoarthritis (degenerative joint disease) and rheumatoid arthritis.
  • osteoarthritis refers to chronic joint disease characterized by the degeneration, destruction and bone hyperplasia of articular cartilage.
  • primary osteoarthritis When the cause of osteoarthritis is known, it is called “secondary osteoarthritis”. Secondary osteoarthritis is caused by other diseases or conditions. Conditions that can lead to secondary osteoarthritis include repeated damage to joint structures or surgery, joint abnormalities at birth (congenital abnormalities), gout, diabetes, and other hormonal disorders.
  • Other forms of arthritis include systemic diseases such as rheumatoid arthritis and systemic lupus erythematosus.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for preventing, treating, delaying and/or reducing arthritis or joint damage; or, the present invention
  • a method for preventing, treating, delaying and/or reducing arthritis or joint damage is provided, which comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the arthritis is selected from osteoarthritis, traumatic arthritis, and autoimmune arthritis.
  • the joint injury is a meniscus injury.
  • the mesenchymal stem cell population is used to prevent, treat, delay, and/or reduce osteoarthritis (OA) in a subject.
  • OA osteoarthritis
  • the mesenchymal stem cell population can improve motor activity, inhibit nerve-generated pain, treat tissue damage or/and relieve symptoms of arthritis.
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration is by intra-articular injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the pharmaceutical composition comprises a cell sphere formed from the population of mesenchymal stem cells. In certain embodiments, the pharmaceutical composition comprises a mixture of the cell sphere and biological material.
  • the mesenchymal stem cell population may be transplanted in the form of a suspension, gel, colloid, slurry or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the drug may also contain another active ingredient (e.g., another therapeutic agent for treating osteoarthritis).
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 No less than 5 ⁇ 10 4 , no less than 7 ⁇ 10 4 , no less than 1 ⁇ 10 5 , no less than 3 ⁇ 10 5 , no less than 5 ⁇ 10 5 , no less 7 ⁇ 10 5 pieces, not less than 1 ⁇ 10 6 pieces, not less than 3 ⁇ 10 6 pieces, not less than 5 ⁇ 10 6 pieces, not less than 7 ⁇ 10 6 pieces, not less than 1 ⁇ 10 7 pieces , Not less than 3 ⁇ 10 7 pieces, not less than 5 ⁇ 10 7 pieces, not less than 7 ⁇ 10 7 pieces, not less than 1 ⁇ 10 8 pieces, not less than 3 ⁇ 10 8 pieces, not less than 5 ⁇ 10 8 pieces, not less than 7 ⁇ 10 8 pieces, not less than 1 ⁇ 10 9 pieces, not less than 3 ⁇ 10 9 pieces, not less than 5 ⁇ 10 9 pieces, not less than 7 ⁇ 10 9 pieces, Not less than 1 ⁇ 10 4 (for example
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • the meniscus is one of the important structures of the knee joint. It is two meniscus-shaped fibrocartilage, located between the femoral condyle and the tibial plateau. Its lateral edge is thicker and the medial edge is thinner. The medial meniscus is "c"-shaped, and the outer side The meniscus is approximately in the shape of an "o".
  • Meniscus injury refers to the rupture of the meniscus caused by factors such as rotation force, squeeze, and the disease of the meniscus itself. It is manifested as severe pain in the knee joint, inability to straighten, swelling, etc. It is one of the most common knee injuries. Meniscus injury of the knee joint is manifested as limited knee joint pain, and some patients have soft legs or interlocking knee joints.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for preventing, treating, delaying and/or reducing meniscus damage; or, the present invention provides prevention , A method for treating, delaying and/or reducing meniscus damage, which comprises administering to a subject in need thereof a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant.
  • the mesenchymal stem cell population can reduce knee joint pain, reduce local edema, relieve claudication, relieve interlocking, or/and relieve pain.
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • transplantation via cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In some preferred schemes, it can be administered intravenously.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the medicament may also contain another active ingredient (for example, another therapeutic agent for treating meniscus injury).
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 No less than 5 ⁇ 10 4 , no less than 7 ⁇ 10 4 , no less than 1 ⁇ 10 5 , no less than 3 ⁇ 10 5 , no less than 5 ⁇ 10 5 , no less 7 ⁇ 10 5 pieces, not less than 1 ⁇ 10 6 pieces, not less than 3 ⁇ 10 6 pieces, not less than 5 ⁇ 10 6 pieces, not less than 7 ⁇ 10 6 pieces, not less than 1 ⁇ 10 7 pieces , Not less than 3 ⁇ 10 7 pieces, not less than 5 ⁇ 10 7 pieces, not less than 7 ⁇ 10 7 pieces, not less than 1 ⁇ 10 8 pieces, not less than 3 ⁇ 10 8 pieces, not less than 5 ⁇ 10 8 pieces, not less than 7 ⁇ 10 8 pieces, not less than 1 ⁇ 10 9 pieces, not less than 3 ⁇ 10 9 pieces, not less than 5 ⁇ 10 9 pieces, not less than 7 ⁇ 10 9 pieces, Not less than 1 ⁇ 10 4 (for example
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • Bone injury is a disease of the motor system, which refers to bone defect or defect repair caused by congenital or acquired factors, as well as complete or partial fracture of the continuity of the bone structure.
  • Such as fractures often include multiple fractures, pelvic fractures, femoral fractures, clavicle fractures, femoral neck fractures, hip fractures, thoracolumbar fractures, compression fractures caused by osteoporosis, ulna fractures, calcaneal fractures, and distal radius fractures , Tibial shaft fractures, tibial plateau fractures, femoral intertrochanteric fractures, ankle fractures, lower limb fractures, long bone shaft fractures, spine fractures and severe open fractures.
  • Bone defects are bone shortages caused by trauma or surgery or trauma, such as trauma, inflammation, bone disease and other factors caused by comminuted fractures, open fractures and large bone tissue defects, osteonecrosis due to inflammation, detachment, bone infarction or Defects caused by avascular necrosis of bone, etc., are all bone defects caused by diseases. Bone defects caused by surgery and traumatic fractures that pass through the limbs or that occur when inactive bone is removed during open fracture debridement are also bone defects. Bone injury has different symptoms depending on the location of the injury. The main manifestations are pain, swelling, and restricted mobility.
  • the patient feels tearing and brittleness, local pain in the knee joint, tenderness, and inability to fully extend the knee, and there is a noise in the knee joint during exercise.
  • the symptoms of joint pain are alleviated, but the knee joint may be softened, and the pain may be aggravated when going up and down, and it may get better after rest.
  • Long-term may be accompanied by traumatic arthritis, quadriceps atrophy.
  • Some patients may also have symptoms of interlocking knee joints.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicine for preventing, treating, delaying and/or reducing bone damage; or, the present invention provides prevention,
  • the method for treating, delaying and/or reducing bone damage includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or its culture supernatant to a subject in need thereof.
  • the mesenchymal stem cell population can accelerate the healing of bone damage, inhibit nerve-generated pain, treat tissue damage or/and relieve the symptoms of arthritis.
  • the subject is a mammal, such as a human.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the mesenchymal stem cell population of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration is by intramuscular injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises pharmaceutically acceptable biological materials, including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • pharmaceutically acceptable biological materials including but not limited to collagen scaffolds, Matrigel, skin repair membranes, aminated gelatin, chitosan, silk fibroin, cellulose polylactic acid , Tropoelastin, hyaluronic acid, etc.
  • the pharmaceutical composition comprises a cell sphere formed from the population of mesenchymal stem cells. In certain embodiments, the pharmaceutical composition comprises a mixture of the cell sphere and biological material.
  • the mesenchymal stem cell population can be transplanted in the form of a suspension, gel, colloid, slurry or mixture
  • the mesenchymal stem cell population of the present invention is administered in combination with another active ingredient, so the medicament may also contain another active ingredient (for example, another therapeutic agent for treating bone injury).
  • the mesenchymal stem cells and the additional therapeutic agent are administered simultaneously, separately or sequentially.
  • the population of mesenchymal stem cells and the additional active ingredient are present as separate components or as a single formulation.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 , not less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , Not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 107, no less than 3 ⁇ 10 7 or no less than 5 ⁇ 10 7 or no less than 7 ⁇ 10 7 or no less than 1 ⁇ 10 8 or no less than 3 ⁇ 10 8 pieces, and Less than 5 ⁇ 10 8 pieces, not less than 7 ⁇ 10 8 pieces, not less than 1 ⁇ 10 9 pieces, not less than 3 ⁇ 10 9 pieces, not less than 5 ⁇ 10 9 pieces, not less than 7 ⁇ 10 9 , not less than
  • the unit dose of the drug contains 1 ⁇ 10 4 to 1 ⁇ 10 10 (for example, 1 ⁇ 10 6 to 1 ⁇ 10 8 , 1 ⁇ 10 6 to 1 ⁇ 10 7 , or 1 ⁇ 10 6 to 5 ⁇ 10 6 ) the mesenchymal stem cells.
  • Mucosal immune system refers to the lymphatic tissues widely distributed in the respiratory tract, gastrointestinal tract, genitourinary tract submucosa and some exocrine glands. It is the main place to perform local specific immune functions.
  • the mucosal immune system consists of four parts: intestinal mucosa-associated lymphoid tissue (GALT), bronchial mucosal-associated lymphoid tissue (BALT), conjunctival-associated lymphoid tissue (CALT), and urogenital mucosa-associated lymphoid tissue (UALT). They are involved in antiviral immunity The reaction plays a very important role.
  • mucosa-associated lymphoid tissue refers to the mucosal epithelium of the respiratory tract, digestive tract, urogenital tract and some exocrine glands (Hard’s gland, pancreas, breast, lacrimal duct, salivary gland secretory duct, etc.) distributed and widely present under the epithelium Lymphatic tissue is the site where the mucous membranes contact and take up antigens and the initial immune response.
  • gastrointestinal mucosal injury gastrointestinal infection, gastritis, enteritis, etc.
  • urethral and reproductive tract related diseases urinary tract infection, urethral mucosal inflammation, reproductive tract infection and related inflammation, etc.
  • oral mucosal disease oral mucosal infection, etc.
  • sexual diseases oral mucosal allergic diseases, oral mucosal ulcer diseases, oral mucosal bullous diseases, oral mucosal marking diseases, oral mucosal granuloma diseases, lips and tongue diseases, sexually transmitted diseases, oral mucosal pigment abnormalities, etc.), medium Ear mucosal inflammation (otitis media, etc.), nasal mucosal disease (sinusitis, olfactory disorders, allergic rhinitis, etc.), respiratory mucosal diseases (chronic obstructive pulmonary disease, asthma, bacterial or viral respiratory diseases), etc.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicament for the prevention and/or treatment of mucosal immune system diseases; or, the present invention provides prevention and/or The method for treating mucosal immune system diseases includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or the culture supernatant thereof to a subject in need thereof.
  • the present invention provides the use of the mesenchymal stem cell population or its culture supernatant in the preparation of a medicament for the prevention and/or treatment of nasal diseases; or, the present invention provides prevention and/or treatment
  • the method for nasal diseases includes administering a preventive and/or therapeutically effective amount of the mesenchymal stem cell population or the culture supernatant thereof to a subject in need thereof.
  • Diseases of nose includes diseases of the external nose, nasal vestibule, nasal cavity and sinuses. It can be divided into infection, bleeding, allergy, tumor, trauma, foreign body, congenital malformation and structural abnormality.
  • the nose is often affected by external adverse factors and is prone to various diseases. Microbial infections can cause inflammation of nasal furuncle, nasal vestibulitis, nasal mucosa and sinuses; the nasal cavity is the gateway for allergens to enter the body and the site where allergic diseases occur, so hay fever and allergic rhinitis are common diseases; Certain oral diseases such as root infections can cause odontogenic maxillary sinusitis.
  • the outer nose is located in the middle of the face and is susceptible to trauma. The outer nose is an important sign to maintain a correct appearance.
  • Nasal cavity and paranasal sinuses are the most common sites for malignant tumors. Maxillary sinus cancer is the most common, followed by nasal cavity cancer and ethmoid sinus cancer.
  • the nose is anatomically adjacent to the cranial cavity, orbital cavity and oral cavity. Diseases of the nasal vestibule, nasal cavity and paranasal sinuses can lead to serious complications, such as meningitis, orbital cellulitis, etc.; blood can cause cavernous sinus infection, severe cases can be blind, or even life threatening
  • nasal mucosa refers to the mucosa covering the surface of the nasal cavity, underneath which is cartilage, bone or skeletal muscle.
  • Common nasal mucosal lesions include sinusitis (the mucous membrane of the sinuses is continuous with the respiratory mucosa, so rhinitis and colds can easily cause sinusitis), olfactory disorders (inflammation, infection or local space-occupying lesions, mucosal swelling, excessive congestion and excessive secretion Many, on the one hand, cause nasal obstruction, block the airflow carrying olfactory, and not reach the olfactory area), allergic rhinitis (called allergic rhinitis, which is the non-nasal mucosa mediated by IgE after the body is exposed to allergens) Infectious inflammatory diseases) and so on.
  • sinusitis the mucous membrane of the sinuses is continuous with the respiratory mucosa, so rhinitis and colds can easily cause sinusitis
  • olfactory disorders
  • the nasal disease is selected from rhinitis, sinusitis, nasal vestibulitis, nasal mucosal disease, or any combination thereof.
  • rhinitis refers to inflammatory diseases of the nasal cavity, which are inflammations of the nasal mucosa caused by viruses, bacteria, allergens, various physical and chemical factors, and certain systemic diseases. Rhinitis is mainly divided into the following four types: chronic rhinitis, acute rhinitis, drug-induced rhinitis, and atrophic rhinitis.
  • Chronic simple rhinitis chronic simple rhinitis, chronic hypertrophic rhinitis, chronic sicca rhinitis, allergic rhinitis (seasonal rhinitis, perennial rhinitis), sicca rhinitis, vasomotor rhinitis, eosinophilic nonallergic rhinitis , Hyperreflective rhinitis, idiopathic rhinitis, structural rhinitis, local allergic rhinitis.
  • long-term chronic diseases such as endocrine disorders, cardiovascular disease, etc., vitamin deficiency, excessive tobacco and alcohol, and long-term use of blood drugs can cause nasal vasodilation and cause symptoms such as rhinitis.
  • Chronic diseases include blood, tuberculosis, diabetes, rheumatism, acute infectious diseases and chronic heart, liver, kidney diseases, etc., which can cause long-term congestion or reflex congestion of the nasal mucosa; chronic inflammation of the nasal cavity and sinuses, or near the infection Influence, promote the occurrence of chronic rhinitis.
  • Allergic rhinitis (Allergic rhinitis, AR), also known as allergic rhinitis, is a common otorhinolaryngology disease and a common respiratory allergic disease.
  • the disease is an allergic disease that occurs in the nasal mucosa, and is characterized by nasal itching, sneezing, rhinorrhea, clear mucus, and swelling of the nasal mucosa.
  • the prevalence of allergic rhinitis is 10%-40%. Pollen allergy is more common in Europe and North America, and perennial allergic rhinitis is more common in Asia. Although allergic rhinitis is not fatal, the patient's nose and general discomfort are obvious, which affects the patient's study and work.
  • Allergic rhinitis is an allergic inflammatory reaction mediated by IgE in the effect of environmental factors in vitro, and the immune response of the nasal mucosa is the main allergic inflammation.
  • the present invention relates to the use of the mesenchymal stem cell population, culture, culture supernatant or pharmaceutical composition as described herein for the prevention and/or treatment of rhinitis (such as allergic rhinitis) in a subject, Or it is prepared to prevent rhinitis in a subject, or delay or reduce rhinitis or prevent alleviation of rhinitis.
  • rhinitis such as allergic rhinitis
  • the drug combination can reduce sneezing caused by rhinitis and reduce the number of times the subject scratches the nose.
  • the drug combination can reduce the level of serum antigen-specific antibody response and reduce the expression of inflammatory mediators.
  • the drug combination can promote angiogenesis in inflammatory sites, promote epithelial cell production, and reduce inflammatory cell infiltration.
  • the drug combination can restore the epithelial surface of the nasal mucosa, normalize cilia, normalize fibroblasts, and normalize cytoplasmic cytoplasm.
  • the subject is a mammal, such as a human.
  • the medicament comprises a therapeutically effective amount of a mesenchymal stem cell population and/or culture and/or a therapeutically effective amount of a culture supernatant as described herein.
  • transplantation is by local injection (for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation), blood circulation route transplantation (for example, intravenous injection transplantation or intraarterial injection transplantation), or transplantation via cerebrospinal fluid route ( For example, lumbar puncture, subarachnoid injection, transplantation, etc., administer the mesenchymal stem cell population or pharmaceutical composition as described herein to the subject.
  • local injection for example, stereotactic intracerebral injection transplantation or spinal cord local injection transplantation
  • blood circulation route transplantation for example, intravenous injection transplantation or intraarterial injection transplantation
  • cerebrospinal fluid route for example, lumbar puncture, subarachnoid injection, transplantation, etc.
  • the medicament of the present invention can be administered by intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, oral administration and the like. In certain preferred embodiments, the administration is by intravenous injection.
  • the pharmaceutical composition may be in any form known in the medical field.
  • the pharmaceutical composition may be tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, freeze-dried Powder) and other forms.
  • the pharmaceutical composition is an injection (including injection solution and lyophilized powder).
  • the pharmaceutical composition comprises a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution (e.g., balanced salt solution or physiological saline), dispersion, suspension or emulsion.
  • the pharmaceutical composition comprises the aforementioned biological carrier or pharmaceutically acceptable biological material, including but not limited to collagen scaffold, Matrigel, skin repair membrane, aminated gelatin, chitosan, silk fibroin, Cellulose polylactic acid, tropoelastin, hyaluronic acid, etc.
  • the drug can be transplanted in the form of a suspension, gel, colloid, slurry, or mixture.
  • the medicament further comprises a carrier or excipient.
  • the carrier is selected from gelatin, chitosan, sodium alginate, collagen, silk protein, cellulose, fibrin, polylactic acid, polyurethane, polyethylene oxide, polyethylene glycol, poly Lactate glycolic acid, poly ⁇ -caprolactone, silicate, silicone rubber, extracellular matrix, decellularized scaffold, or any combination thereof.
  • the carrier is selected from gelatin, collagen, or any combination thereof.
  • the medicament further comprises a second active ingredient.
  • the second active ingredient is selected from glucocorticoids, nasal decongestants, antihistamines (such as azelastine), leukotriene receptor antagonists (such as montelukast Sodium), anticholinergic drugs (such as ipratropium bromide), anti-allergic drugs (such as sodium cromoside), mucolytic drugs (such as myrtle oil), antibacterial drugs, or any combination thereof.
  • antihistamines such as azelastine
  • leukotriene receptor antagonists such as montelukast Sodium
  • anticholinergic drugs such as ipratropium bromide
  • anti-allergic drugs such as sodium cromoside
  • mucolytic drugs such as myrtle oil
  • antibacterial drugs or any combination thereof.
  • the glucocorticoid is selected from beclomethasone propionate, budesonide, fluticasone propionate, mometasone furoate, or any combination thereof.
  • the antibacterial agent is selected from amoxicillin, cefpodoxime axetil, cefuroxime axetil, cefdinir, trimethoprim, sulfamethoxazole, doxycycline, azithromycin, clarithromycin , Erythromycin, gatifloxacin, levofloxacin, moxifloxacin, ceftriaxone or any combination thereof.
  • the drug is in a unit dosage form, and the unit dose of the drug contains not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4, not less than 1 ⁇ 10 4 ). Less than 5 ⁇ 10 4 , not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 10 7 , not less than 3 ⁇ 10 7 , not less than 5 ⁇ 10 7 , not less than 7 ⁇ 10 7 , not less than 1 ⁇ 10 8 , not less than 3 ⁇ 10 8 , not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 10 9 , Not less than 3 ⁇ 10 9 , not less than 5 ⁇ 10 9 , not less than 7 ⁇ 10 8 , not
  • the administered dose of the mesenchymal stem cells is not less than 1 ⁇ 10 4 (for example, not less than 1 ⁇ 10 4 , not less than 3 ⁇ 10 4 , not less than 5 ⁇ 10 4 , Not less than 7 ⁇ 10 4 , not less than 1 ⁇ 10 5 , not less than 3 ⁇ 10 5 , not less than 5 ⁇ 10 5 , not less than 7 ⁇ 10 5 , not less than 1 ⁇ 10 6 , not less Less than 3 ⁇ 10 6 , not less than 5 ⁇ 10 6 , not less than 7 ⁇ 10 6 , not less than 1 ⁇ 10 7 , not less than 3 ⁇ 10 7 , not less than 5 ⁇ 10 7 , not less than 7 ⁇ 10 7 , not less than 1 ⁇ 10 8 , not less than 3 ⁇ 10 8 , not less than 5 ⁇ 10 8 , not less than 7 ⁇ 10 8 , not less than 1 ⁇ 10 9 , not less than 3 ⁇ 10 9 , not less than 5 ⁇ 10 9 , not less than 7 ⁇ 10 9 , not less than 1 ⁇ 10 10
  • the route of administration of the mesenchymal stem cells is selected from injection administration, smear administration, paste administration, enema administration, perfusion administration, rectal administration, and oral administration.
  • the method further comprises administering a second active ingredient to a subject in need thereof, the second active ingredient being as described or defined above.
  • the subject is a mammal, such as a human.
  • the present invention provides a product for treating nasal diseases, which comprises a first active ingredient mesenchymal stem cell population.
  • the mesenchymal stem cell population is as described or defined previously.
  • the nasal disease is as previously described or defined.
  • the product further comprises a second active ingredient.
  • the second active ingredient is as previously described or defined.
  • the first active ingredient and the second active ingredient are present alone or in combination.
  • the first active ingredient is administered in combination with a second active ingredient selected from the foregoing.
  • the product is an implant.
  • the implant is used to improve the microenvironment and suppress immune rejection.
  • the subject is a mammal, such as a human.

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CN114317441A (zh) * 2021-12-30 2022-04-12 广西医科大学 肝癌模型细胞、体外培养方法、应用及肝癌动物模型建立方法
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WO2024019962A1 (en) * 2022-07-18 2024-01-25 Astellas Institute For Regenerative Medicine Methods of treating brain injury
CN115364201A (zh) * 2022-10-24 2022-11-22 深圳博雅感知医疗科技有限公司 治疗卵巢早衰的骨髓浓缩细胞制剂组合物
CN115364201B (zh) * 2022-10-24 2023-02-03 深圳博雅感知医疗科技有限公司 治疗卵巢早衰的骨髓浓缩细胞制剂组合物
CN116189765A (zh) * 2023-02-23 2023-05-30 上海捷易生物科技有限公司 一种iPS细胞遗传学风险评估系统及应用
CN116189765B (zh) * 2023-02-23 2023-08-15 上海捷易生物科技有限公司 一种iPS细胞遗传学风险评估系统及应用

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